Raadpleeg ook de literatuurlijsten van niet-toxische middelen en behandelingen van arts-bioloog drs. Engelbert Valstar

1 mei 2019: Bron: . 2019 Feb; 54(2): 407–419

De afgelopen tientallen jaren hebben oncologen zich gefocust op het behandelen van de tumoren, maar de behandelingen kunnen resulteren in schade aan de tumor dragende gastheer (de kankerpatiënt) en zijn immuunsysteem, oftewel een verslechterende kwaliteit van leven, die soms zo slecht is dat mensen het amper nog kunnen dragen. De bijwerkingen van systemische chemotherapie voor de behandeling van kanker zijn namelijk vaak ernstig en soms chronisch.

Om er een paar te noemen alleen al bij borstkankerpatienten die chemotherapie krijgen bevestigen onderstaande studies dat chemotherapie soms chronische ernstige bijwerkingen kan veroorzaken. (met dank aan Jolanda die ons hierop wees): 

(1) https://www.theguardian.com/society/2014/apr/25/having-cancer-not-fight-or-battle

(2) https://www.sciencedirect.com/science/article/pii/S152682091170297X

(3) https://ascopubs.org/doi/full/10.1200/JCO.2016.68.5826

(4) https://www.ncbi.nlm.nih.gov/pubmed/21430504

(5) https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5256170/

(6) https://www.ncbi.nlm.nih.gov/pubmed/15630849 

De laatste jaren is er veel aandacht besteed aan het immuunsysteem van patiënten en de activering ervan via biologische therapieën. Biologische therapieën, waaronder immuuntherapie en behandelingen met gemoduleerde oncolytische virussen (OV- therapie),. Deze vormen van behandelingen zijn vaak meer fysiologisch en worden beter verdragen door kankerpatiënten.

Waarbij opvalt dat immuuntherapie met gemoduleerde virussen veruit de minste bijwerkingen geeft met graad 0 tot 2. En ook vaak de beste resultaten, indien ingezet in een vroeg stadium van de ziekte.

Chemotherapeutische cytostatica (chemokuren) en SMI's zijn chemische behandelingen, terwijl de andere behandelingen biologisch zijn. De werkingsmechanismen en bijwerkingen van deze geneesmiddelen worden gepresenteerd in onderstaande Table I.

Table I

Overview of chemotherapy and biological cancer therapy.

Type of therapyC or BMechanism of actionPhysiologicalSide effects
1. Cytostatic drugs C Interfere with cell proliferation No Grade 1-4
2. Small molecule inhibitorsa C Targeted therapy: Interfere with oncogenic signal transduction Yes Grade 1-4
3. Antitumor MAbsb B Targeted immunotherapy Yes Grade 1-3
4. Anti-angiogenesis MAbsc B Inhibit angiogenesis Yes Grade 1-3
5. Checkpoint inhibitor MAbsd B Immune regulation No Grade 1-4
6. CAR-T cells B Targeted cytotoxic T lymphocytes No Grade 1-3
7. Antitumor vaccines B Active specific vaccination Yes Grade 0-2
8. Oncolytic virusese B Oncolysis, induction of immunogenic cell death Yes Grade 0-2
ae.g. KIT inhibitors, such as sunitinib, imatinib, sorafenib and lapatinib;
be.g. cetuximab, trastuzumab, panitumumab (targets include HER-1, HER-2 and RAS);
ce.g. bevacizumab (Avastin; targets VEGF-L), ramucirumab (Cyramza; targets VEGF receptor 2);
de.g. ipilimumab (targets cytotoxic T-lymphocyte-associated protein 4), nivolumab (targets programmed cell death protein 1), atezolizumab and durvalumab (targets programmed death-ligand 1);
ee.g. RNA viruses, including Newcastle Disease Virus from attenuated natural wild type strains. B, biological therapy; C, chemoteherapy; HER, human epidermal growth factor receptor; VEGF, vascular endothelial growth factor.

Met betrekking tot SMI's werd geconcludeerd dat ze fysiologisch waren, aangezien SMI's een op tumoren gerichte aanpak voorstellen; toch kunnen normale cellen ook worden beïnvloed. Met betrekking tot anti-PD medicijnen , de MAbs, werd geconcludeerd dat ze niet fysiologisch waren, omdat interferentie met immuunregulatie ook interfereert met auto-immuunreactiviteit. Met betrekking tot CAR-T-cellen werd geconcludeerd dat ze niet fysiologisch waren, omdat de receptor kunstmatig is en alle cellen dezelfde receptor hebben.

Het veranderen van de manier hoe kanker te behandelen is echter niet eenvoudig, want de gezondheidszorg is een enorme markt. En het systeem van evidence based medicine is nog te weinig aangepast aan niuewere vormen van behandelen, waardoor het te leveren bewijs van efectiviteit veel te lang duurt en te duur wordt. 
Op dit moment zijn er medicijnen met een immuuntherapeutische werking, zoals MAbs en anti-PD medicijnen - checkpointremmers met succes op de markt gekomen; echter ook tegen bijna onbetaalbare prijzen. dit is echter maar een klein deel van het potentieel van wat mogelijk is met immuuntherapie.

In de toekomst kan immuuntherapie een op zichzelf staande discipline worden, waaronder immuundiagnose, immunotherapie, immuunbewaking en immunologische follow-up. Verder zijn twee kankervaccins, ATV-NDV en VOL-DC, die OV's combineren met TAA's, in de klinische toepassing opgenomen. Na> 30 jaar kan integratie van OV's in kankerimmuuntherapie snel mainstream worden ()

Bovenstaande teksten komen uit een grote reviewstudie: From chemotherapy to biological therapy: A review of novel concepts to reduce the side effects of systemic cancer treatment (Review) welke volledig gratis is in te zien. 

Het studierapport geeft een uitstekend gedocumenteerd beeld met een waardevolle referentielijst. Hier de conclusie / toelichting en abstract. Klik op de verschillende hoofdstukken om het studierapport door te bladeren

Biological and physiological therapies, which support the immune system, may therefore benefit cancer treatment. The present review focused on immunotherapy, with the aim of reducing side effects and increasing long-lasting efficacy in cancer therapy.

. 2019 Feb; 54(2): 407–419.
Published online 2018 Dec 10. doi: 10.3892/ijo.2018.4661
PMCID: PMC6317661
PMID: 30570109

From chemotherapy to biological therapy: A review of novel concepts to reduce the side effects of systemic cancer treatment (Review)

Abstract

The side effects of systemic chemotherapy used to treat cancer are often severe. For decades, oncologists have focused on treating the tumor, which may result in damage to the tumor-bearing host and its immune system. Recently, much attention has been paid to the immune system of patients and its activation via biological therapies. Biological therapies, including immunotherapy and oncolytic virus (OV) therapy, are often more physiological and well tolerated. The present review elucidated how these therapies work and why these therapies may be better tolerated: i) In contrast to chemotherapy, immunotherapies induce a memory function of the adaptive immunity system; ii) immunotherapies aim to specifically activate the immune system against cancer; side effects are low due to immune tolerance mechanisms, which maintain the integrity of the body in the presence of B and T lymphocytes with their antigen-receptor specificities and; iii) the type I interferon response, which is evoked by OVs, is an ancient innate immune defense system. Biological and physiological therapies, which support the immune system, may therefore benefit cancer treatment. The present review focused on immunotherapy, with the aim of reducing side effects and increasing long-lasting efficacy in cancer therapy.

10. Discussion

In spite of its severe side effects, chemotherapy remains a main treatment option for cancer. As early as 1963, the disappointing efficacy of chemotherapy was reported (). However, between 1984 and 1985, at the peak of aggressive chemotherapy, >6,000 articles were published in medical journals regarding treatment of cancer with chemotherapy; none of these studies reported on novel strategies that could cure advanced solid tumors in combination with chemotherapy (). Grade 3 and 4 side effects can be life threatening. One of the many types of cytostatic drug that produce such side effects are molecular derivatives of nitrogen mustard, which is a toxin that was used during World War I. Examples, still in use, are melphalan, chlorambucil, cyclophosphamide, ifosfamid and others.

Evidence-based medicine is currently the gold standard for the approval of novel drugs. The quality of criteria for clinical studies has steadily increased since the introduction of cytostatic drugs; however, some drugs originally approved many years ago are still in use. Recommendations for updates of standard therapy come from medical oncology societies. There is no guarantee, however, that such recommendations are devoid of conflicts of interest; therefore, it remains the individual responsibility of a medical oncologist to decide which drugs to apply or not. Medical ethics should be respected.

To change the direction of cancer therapy is not easy, as healthcare is a huge market. At present, immunological products, such as MAbs and checkpoint inhibitors have successfully entered the market; however, this is only a small portion of the potential of immunotherapy. In the future, immunotherapy may be a discipline in its own right, including immune diagnosis, immunotherapy, immune monitoring and immunological follow-up. Furthermore, two cancer vaccines, ATV-NDV and VOL-DC, which combine OVs with TAAs, have been entered into clinical application. After >30 years, integrating OVs into cancer immunotherapy may soon become mainstream ().

11. Conclusions

The present review compared chemotherapy and biological therapies, including immunotherapy and OV therapy.

Systemic forms of cancer treatment are necessary at the transition phase of cancer, when it turns from a localized into a systemic form of disease with metastases. Systemic forms of cancer treatment can be prophylactic (e.g. in a post-operative situation) or therapeutic. The primary aim of chemotherapy is to reduce tumor burden, whereas the aim of immunotherapy is to generate systemic protective anticancer immunity. The focus is either on the tumor or on the tumor-bearing host organism and its immune system.

The aim of this review was to present novel concepts, which may reduce side effects from systemic cancer treatment. This is necessary because chemotherapy often exhibits relatively low tumor specificity and high toxicity. Targeted therapy with chemically designed SMIs has higher tumor specificity than conventional chemotherapy; however, the side effects are similar. The majority of novel concepts are derived from biological types of therapy (Tables IIII); some of these biological therapies exert considerable side effects. Conversely, conventional immunotherapy, including vaccination and OV therapy, exerts only mild side effects and is well tolerated. It is suggested that the reason for this difference is physiological: Immunological self-tolerance and immunological memory.

An important difference between chemotherapy and immunotherapy or OV therapy is the dose-response curve. While in the case of cytostatic drugs the curve is linear, in the case of biological and physiological therapies it is bell-shaped. The reason for this difference appears to be due to the complementarity of specific cognate molecular lock-and-key interactions. This is exemplified with interactions between antigens and antibodies, as well as between pMHC and TCR in cases of T-cell-mediated immune responses.

Notably, a combination of cancer immunotherapy and OV therapy was successful in a randomized controlled study (,). This previous study evaluated the efficacy of post-operative vaccination with ATV-NDV in patients with stage IV CRC following resection of liver metastases. The results revealed that in patients with colon cancer a significant 10-year survival benefit of as much as 30% was detected. The magnitude of the effect is similar to that obtained in patients with melanoma treated with ICB (). The side effects of these two approaches, however, were different: Grade 0-2 for the vaccination study compared with grade 1-4 for the ICB study.

With regards to future developments, it has been suggested to combine vaccines, OVs and immune checkpoint inhibitors to prime, expand and facilitate effective tumor immunotherapy (,). The main conclusions of this review are: i) It may be beneficial for immunotherapy to be included in standard care. Rules of evidence-based medicine should be adjusted to the needs of individualized immunotherapy studies, as well as to multimodal therapy studies in general. ii) Recommendations for the use of cytostatic drugs that produce severe side effects and low efficacy should be reviewed by societies of internal medicine.

Acknowledgments

Chapter 6 on central immunological self-tolerance in the thymus is dedicated to the author’s former colleague at the DKFZ (Heidelberg, Germany), the late Professor Bruno Kyewski (1950-2018). The author also wishes to acknowledge Dr Wilfried Stuecker and Dr Stefaan van Gool (IOZK, Cologne, Germany) for their support in translational immunotherapy.

Funding

This review was supported by IOZK, Cologne, Germany.

Availability of data and materials

Not applicable.

Author contributions

VS contributed the idea, wrote the text, and generated the tables.

Ethics approval and consent to participate

Not applicable.

Patient consent for publication

Not applicable.

Competing interests

The author declares that they have no competing interests.

References

1. Halstedt WS. In: Surgical Papers. Burket WC, editor. Vol. 2. Baltimore: 1924. []
2. Fisher B, Wolmark N. The current status of systemic adjuvant therapy in the management of primary breast cancer. Surg Clin North Am. 1981;61:1347–1360. doi: 10.1016/S0039-6109(16)42589-2. [PubMed] [CrossRef] []
3. Mukherjee S. The Emperor of All Maladies: A Biography of Cancer. Scribner, a Division of Simon and Schuster Inc.; New York: 2010. []
4. Schirrmacher V. Quo Vadis Cancer Therapy? Fascinating discoveries of the last 60 years. Lambert Academic Publishing; 2017. pp. 1–353. []
5. Koeppen BM, Stanton BA, editors. Berne and Levy Physiology. 7th edition. Elsevier; Amsterdam: 2018. p. 880. []
6. Seeber S, Schütte J, editors. Therapiekonzepte Onkologie. Springer-Verlag; Berlin, Heidelberg: 1993. [CrossRef] []
7. Morgan G, Ward R, Barton M. The contribution of cytotoxic chemotherapy to 5-year survival in adult malignancies. Clin Oncol (R Coll Radiol) 2004;16:549–560. doi: 10.1016/j.clon.2004.06.007. [PubMed] [CrossRef] []
8. Steward BW, Wild CW, editors. World Cancer Report. IARC Press; Lyon: 2014. p. 2014. []
9. American Cancer Society . Cancer Facts and Figures 2018. American Cancer Society, Inc.; Atlanta, GA: 2018. []
10. Niraula S, Seruga B, Ocana A, Shao T, Goldstein R, Tannock IF, Amir E. The price we pay for progress A meta-analysis of harms of newly approved anticancer drugs. J Clin Oncol. 2012;30:3012–3019. doi: 10.1200/JCO.2011.40.3824. [PubMed] [CrossRef] []
11. Niraula S, Amir E, Vera-Badillo F, Seruga B, Ocana A, Tannock IF. Risk of incremental toxicities and associated costs of new anticancer drugs: A meta-analysis. J Clin Oncol. 2014;32:3634–3642. doi: 10.1200/JCO.2014.55.8437. [PubMed] [CrossRef] []
12. Barnes TA, Amir E, Templeton AJ, Gomez-Garcia S, Navarro B, Seruga B, Ocana A. Efficacy, safety, tolerability and price of newly approved drugs in solid tumors. Cancer Treat Rev. 2017;56:1–7. doi: 10.1016/j.ctrv.2017.03.011. [PubMed] [CrossRef] []
13. Reid E, Suneja G, Ambinder RF, Ard K, Baiocchi R, Barta SK, Carchman E, Cohen A, Gupta N, Johung KL, et al. Cancer in people living with HIV, version 1.2018, NCCN clinical practice guidelines in oncology. J Natl Compr Canc Netw. 2018;16:986–1017. doi: 10.6004/jnccn.2018.0066. [PubMed] [CrossRef] []
14. Gutierrez-Dalmau A, Campistol JM. Immunosuppressive therapy and malignancy in organ transplant recipients: A systematic review. Drugs. 2007;67:1167–1198. doi: 10.2165/00003495-200767080-00006. [PubMed] [CrossRef] []
15. Zhang L, Conejo-Garcia JR, Katsaros D, Gimotty PA, Massobrio M, Regnani G, Makrigiannakis A, Gray H, Schlienger K, Liebman MN, et al. Intratumoral T cells, recurrence, and survival in epithelial ovarian cancer. N Engl J Med. 2003;348:203–213. doi: 10.1056/NEJMoa020177. [PubMed] [CrossRef] []
16. Clemente CG, Mihm MC, Jr, Bufalino R, Zurrida S, Collini P, Cascinelli N. Prognostic value of tumor infiltrating lymphocytes in the vertical growth phase of primary cutaneous melanoma. Cancer. 1996;77:1303–1310. doi: 10.1002/(SICI)1097-0142(19960401)77:7<1303::AID-CNCR12>3.0.CO;2-5. [PubMed] [CrossRef] []
17. Lipponen PK, Eskelinen MJ, Jauhiainen K, Harju E, Terho R. Tumour infiltrating lymphocytes as an independent prognostic factor in transitional cell bladder cancer. Eur J Cancer. 1992;29A:69–75. [PubMed] []
18. Naito Y, Saito K, Shiiba K, Ohuchi A, Saigenji K, Nagura H, Ohtani H. CD8+ T cells infiltrated within cancer cell nests as a prognostic factor in human colorectal cancer. Cancer Res. 1998;58:3491–3494. [PubMed] []
19. Sommerfeldt N, Schütz F, Sohn C, Förster J, Schirrmacher V, Beckhove P. The shaping of a polyvalent and highly individual T-cell repertoire in the bone marrow of breast cancer patients. Cancer Res. 2006;66:8258–8265. doi: 10.1158/0008-5472.CAN-05-4201. [PubMed] [CrossRef] []
20. Feuerer M, Beckhove P, Bai L, Solomayer EF, Bastert G, Diel IJ, Pedain C, Oberniedermayr M, Schirrmacher V, Umansky V. Therapy of human tumors in NOD/SCID mice with patient-derived reactivated memory T cells from bone marrow. Nat Med. 2001;7:452–458. doi: 10.1038/86523. [PubMed] [CrossRef] []
21. Böhle A, Brandau S. Immune mechanisms in bacillus Calmette-Guerin immunotherapy for superficial bladder cancer. J Urol. 2003;170:964–969. doi: 10.1097/01.ju.0000073852.24341.4a. [PubMed] [CrossRef] []
22. Khong HT, Restifo NP. Natural selection of tumor variants in the generation of ‘tumor escape’ phenotypes. Nat Immunol. 2002;3:999–1005. doi: 10.1038/ni1102-999. [PMC free article] [PubMed] [CrossRef] []
23. Teng MW, Galon J, Fridman WH, Smyth MJ. From mice to humans: Developments in cancer immunoediting. J Clin Invest. 2015;125:3338–3346. doi: 10.1172/JCI80004. [PMC free article] [PubMed] [CrossRef] []
24. Zhang AW, McPherson A, Milne K, Kroeger DR, Hamilton PT, Miranda A, Funnell T, Little N, de Souza CPE, Laan S, et al. Interfaces of malignant and immunologic clonal dynamics in ovarian cancer. Cell. 2018;173:1755–1769. e22. doi: 10.1016/j.cell.2018.03.073. [PubMed] [CrossRef] []
25. Bäumler E, Ehrlich Paul. Forscher für das Leben. Bastei-Lübbe-Taschenbuch. 1989;61:163. []
26. Pauling L, Delbrück M. The nature of the intermolecular forces operative in biological processes. Science. 1940;92:77–79. doi: 10.1126/science.92.2378.77. [PubMed] [CrossRef] []
27. Rudolph MG, Stanfield RL, Wilson IA. How TCRs bind MHCs, peptides, and coreceptors. Annu Rev Immunol. 2006;24:419–466. doi: 10.1146/annurev.immunol.23.021704.115658. [PubMed] [CrossRef] []
28. Manz BN, Jackson BL, Petit RS, Dustin ML, Groves J. T-cell triggering thresholds are modulated by the number of antigen within individual T-cell receptor clusters. Proc Natl Acad Sci USA. 2011;108:9089–9094. doi: 10.1073/pnas.1018771108. [PMC free article] [PubMed] [CrossRef] []
29. Reinherz EL. αβ TCR-mediated recognition: Relevance to tumor-antigen discovery and cancer immunotherapy. Cancer Immunol Res. 2015;3:305–312. doi: 10.1158/2326-6066.CIR-15-0042. [PMC free article] [PubMed] [CrossRef] []
30. Crespo J, Sun H, Welling TH, Tian Z, Zou W. T cell anergy, exhaustion, senescence, and stemness in the tumor microenvironment. Curr Opin Immunol. 2013;25:214–221. doi: 10.1016/j.coi.2012.12.003. [PMC free article] [PubMed] [CrossRef] []
31. Boissonnas A, Fetler L, Zeelenberg IS, Hugues S, Amigorena S. In vivo imaging of cytotoxic T cell infiltration and elimination of a solid tumor. J Exp Med. 2007;204:345–356. doi: 10.1084/jem.20061890. [PMC free article] [PubMed] [CrossRef] []
32. Otto L, Zelinskyy G, Schuster M, Dittmer U, Gunzer M. Imaging of cytotoxic antiviral immunity while considering the 3R principle of animal research. J Mol Med (Berl) 2018;96:349–360. doi: 10.1007/s00109-018-1628-7. [PubMed] [CrossRef] []
33. Vasaturo A, Di Blasio S, Peeters DG, de Koning CC, de Vries JM, Figdor CG, Hato SV. Clinical implications of co-inhibitory molecule expression in the tumor microenvironment for DC vaccination: A game of stop and go. Front Immunol. 2013;4:417. doi: 10.3389/fimmu.2013.00417. [PMC free article] [PubMed] [CrossRef] []
34. Teng MW, Ngiow SF, Ribas A, Smyth MJ. Classifying cancers based on T-cell infiltration and PD-L1. Cancer Res. 2015;75:2139–2145. doi: 10.1158/0008-5472.CAN-15-0255. [PMC free article] [PubMed] [CrossRef] []
35. Lindenmann J. Viral oncolysis with host survival. Proc Soc Exp Biol Med. 1963;113:85–91. doi: 10.3181/00379727-113-28284. [PubMed] [CrossRef] []
36. Cassel WA, Garrett RE. Tumor immunity after viral oncolysis. J Bacteriol. 1966;92:792. [PMC free article] [PubMed] []
37. Heicappell R, Schirrmacher V, von Hoegen P, Ahlert T, Appelhans B. Prevention of metastatic spread by postoperative immunotherapy with virally modified autologous tumor cells. I. Parameters for optimal therapeutic effects. Int J Cancer. 1986;37:569–577. doi: 10.1002/ijc.2910370416. [PubMed] [CrossRef] []
38. Ertel C, Millar NS, Emmerson PT, Schirrmacher V, von Hoegen P. Viral hemagglutinin augments peptide-specific cytotoxic T cell responses. Eur J Immunol. 1993;23:2592–2596. doi: 10.1002/eji.1830231032. [PubMed] [CrossRef] []
39. Schirrmacher V, Haas C, Bonifer R, Ertel C. Virus potentiation of tumor vaccine T-cell stimulatory capacity requires cell surface binding but not infection. Clin Cancer Res. 1997;3:1135–1148. [PubMed] []
40. Khazaie K, Prifti S, Beckhove P, Griesbach A, Russell S, Collins M, Schirrmacher V. Persistence of dormant tumor cells in the bone marrow of tumor cell-vaccinated mice correlates with long-term immunological protection. Proc Natl Acad Sci USA. 1994;91:7430–7434. doi: 10.1073/pnas.91.16.7430. [PMC free article] [PubMed] [CrossRef] []
41. Müller M, Gounari F, Prifti S, Hacker HJ, Schirrmacher V, Khazaie K. EblacZ tumor dormancy in bone marrow and lymph nodes: Active control of proliferating tumor cells by CD8+ immune T cells. Cancer Res. 1998;58:5439–5446. [PubMed] []
42. Klug F, Prakash H, Huber PE, Seibel T, Bender N, Halama N, Pfirschke C, Voss RH, Timke C, Umansky L, et al. Low-dose irradiation programs macrophage differentiation to an iNOS+/M1 phenotype that orchestrates effective T cell immunotherapy. Cancer Cell. 2013;24:589–602. doi: 10.1016/j.ccr.2013.09.014. [PubMed] [CrossRef] []
43. Gires O, Seliger B, editors. Tumor-Associated Antigens. Wiley-Blackwell; Hoboken, NJ: 2009. []
44. Tokuyasu TA, Huang JD. A primer on the recent developments in cancer immunotherapy, with a focus on neoantigen vaccines. J Cancer Metastasis Treat. 2018;4:2–24. doi: 10.20517/2394-4722.2017.52. [CrossRef] []
45. Hanahan D, Weinberg RA. The hallmarks of cancer. Cell. 2000;100:57–70. doi: 10.1016/S0092-8674(00)81683-9. [PubMed] [CrossRef] []
46. Flavahan WA, Gaskell E, Bernstein BE. Epigenetic plasticity and the hallmarks of cancer. Science. 2017;357:2380. doi: 10.1126/science.aal2380. [PMC free article] [PubMed] [CrossRef] []
47. Coulie PG, Lehmann F, Lethé B, Herman J, Lurquin C, Andrawiss M, Boon T. A mutated intron sequence codes for an antigenic peptide recognized by cytolytic T lymphocytes on a human melanoma. Proc Natl Acad Sci USA. 1995;92:7976–7980. doi: 10.1073/pnas.92.17.7976. [PMC free article] [PubMed] [CrossRef] []
48. Derbinski J, Kyewski B. How thymic antigen presenting cells sample the body’s self-antigens. Curr Opin Immunol. 2010;22:592–600. doi: 10.1016/j.coi.2010.08.003. [PubMed] [CrossRef] []
49. Kyewski B, Peterson P. Aire, master of many trades. Cell. 2010;140:24–26. doi: 10.1016/j.cell.2009.12.036. [PubMed] [CrossRef] []
50. Delacher M, Imbusch CD, Weichenhan D, Breiling A, Hotz-Wagenblatt A, Träger U, Hofer AC, Kägebein D, Wang Q, Frauhammer F, et al. Genome-wide DNA-methylation landscape defines specialization of regulatory T cells in tissues. Nat Immunol. 2017;18:1160–1172. doi: 10.1038/ni.3799. [PMC free article] [PubMed] [CrossRef] []
51. Sallusto F, Geginat J, Lanzavecchia A. Central memory and effector memory T cell subsets: Function, generation, and maintenance. Annu Rev Immunol. 2004;22:745–763. doi: 10.1146/annurev.immunol.22.012703.104702. [PubMed] [CrossRef] []
52. Di Rosa F, Pabst R. The bone marrow: A nest for migratory memory T cells. Trends Immunol. 2005;26:360–366. doi: 10.1016/j.it.2005.04.011. [PubMed] [CrossRef] []
53. Han SJ, Glatman Zaretsky A, Andrade-Oliveira V, Collins N, Dzutsev A, Shaik J, Morais da Fonseca D, Harrison OJ, Tamoutounour S, Byrd AL, et al. White adipose tissue is a reservoir for memory T cells and promotes protective memory responses to infection. Immunity. 2017;47:1154–1168.e6. doi: 10.1016/j.immuni.2017.11.009. [PMC free article] [PubMed] [CrossRef] []
54. Durek P, Nordström K, Gasparoni G, Salhab A, Kressler C, de Almeida M, Bassler K, Ulas T, Schmidt F, Xiong J, et al. DEEP Consortium: Epigenomic profiling of human CD4+ T cells supports a linear differentiation model and highlights molecular regulators of memory development. Immunity. 2016;45:1148–1161. doi: 10.1016/j.immuni.2016.10.022. [PubMed] [CrossRef] []
55. Gattinoni L, Lugli E, Ji Y, Pos Z, Paulos CM, Quigley MF, Almeida JR, Gostick E, Yu Z, Carpenito C, et al. A human memory T cell subset with stem cell-like properties. Nat Med. 2011;17:1290–1297. doi: 10.1038/nm.2446. [PMC free article] [PubMed] [CrossRef] []
56. Luckey CJ, Bhattacharya D, Goldrath AW, Weissman IL, Benoist C, Mathis D. Memory T and memory B cells share a transcriptional program of self-renewal with long-term hematopoietic stem cells. Proc Natl Acad Sci USA. 2006;103:3304–3309. doi: 10.1073/pnas.0511137103. [PMC free article] [PubMed] [CrossRef] []
57. Gattinoni L, Speiser DE, Lichterfeld M, Bonini C. T memory stem cells in health and disease. Nat Med. 2017;23:18–27. doi: 10.1038/nm.4241. [PMC free article] [PubMed] [CrossRef] []
58. Akondy RS, Fitch M, Edupuganti S, Yang S, Kissick HT, Li KW, Youngblood BA, Abdelsamed HA, McGuire DJ, Cohen KW, et al. Origin and differentiation of human memory CD8 T cells after vaccination. Nature. 2017;552:362–367. doi: 10.1038/nature24633. [PMC free article] [PubMed] [CrossRef] []
59. Wolchok JD, Kluger H, Callahan MK, Postow MA, Rizvi NA, Lesokhin AM, Segal NH, Ariyan CE, Gordon RA, Reed K, et al. Nivolumab plus ipilimumab in advanced melanoma. N Engl J Med. 2013;369:122–133. doi: 10.1056/NEJMoa1302369. [PMC free article] [PubMed] [CrossRef] []
60. Fehrenbacher L, Spira A, Ballinger M, Kowanetz M, Vansteenkiste J, Mazieres J, Park K, Smith D, Artal-Cortes A, Lewanski C, et al. POPLAR Study Group Atezolizumab versus docetaxel for patients with previously treated non-small-cell lung cancer (POPLAR): A multicentre, open-label, phase 2 randomised controlled trial. Lancet. 2016;387:1837–1846. doi: 10.1016/S0140-6736(16)00587-0. [PubMed] [CrossRef] []
61. Allison JP. Checkpoints. Cell. 2015;162:1202–1205. doi: 10.1016/j.cell.2015.08.047. [PubMed] [CrossRef] []
62. Oiseth SJ, Aziz MS. Cancer immunotherapy: A brief review of the history, possibilities, and challenges ahead. J Cancer Metastasis Treat. 2017;3:250–261. doi: 10.20517/2394-4722.2017.41. [CrossRef] []
63. Chamoto K, Al-Habsi M, Honjo T. Role of PD-1 in immunity and diseases. Curr Top Microbiol Immunol. 2017;410:75–97. [PubMed] []
64. Kumar P, Bhattacharya P, Prabhakar BS. A comprehensive review on the role of co-signaling receptors and Treg homeostasis in autoimmunity and tumor immunity. J Autoimmun. 2018 Aug 30; doi: 10.1016/j.jaut.2018.08.007. Epub ahead of print. [PMC free article] [PubMed] [CrossRef] []
65. Schirrmacher V, Beckhove P, Krüger A, Rocha M, Umansky V, Fichtner K, Hull W, Zangemeisterwittke U, Griesbach A, Jurianz K, et al. Effective immune rejection of advanced metastasized cancer. Int J Oncol. 1995;6:505–521. [PubMed] []
66. Schirrmacher V, Beckhove P, Choi C, Griesbach A, Mahnke Y. Tumor-immune memory T cells from the bone marrow exert GvL without GvH reactivity in advanced metastasized cancer. Int J Oncol. 2005;27:1141–1149. [PubMed] []
67. Schirrmacher V. Complete remission of cancer in late-stage disease by radiation and transfer of allogeneic MHC-matched immune T cells: Lessons from GvL studies in animals. Cancer Immunol Immunother. 2014;63:535–543. doi: 10.1007/s00262-014-1530-2. [PubMed] [CrossRef] []
68. Feuerer M, Beckhove P, Garbi N, Mahnke Y, Limmer A, Hommel M, Hämmerling GJ, Kyewski B, Hamann A, Umansky V, et al. Bone marrow as a priming site for T-cell responses to blood-borne antigen. Nat Med. 2003;9:1151–1157. doi: 10.1038/nm914. [PubMed] [CrossRef] []
69. Schirrmacher V, Feuerer M, Fournier P, Ahlert T, Umansky V, Beckhove P. T-cell priming in bone marrow: The potential for long-lasting protective anti-tumor immunity. Trends Mol Med. 2003;9:526–534. doi: 10.1016/j.molmed.2003.10.001. [PubMed] [CrossRef] []
70. Newick K, O’Brien S, Moon E, Albelda SM. CAR T cell therapy of solid tumors. Annu Rev Med. 2017;68:139–152. doi: 10.1146/annurev-med-062315-120245. [PubMed] [CrossRef] []
71. Chmielewski M, Hombach AA, Abken H. Of CARs and TRUCKs: Chimeric antigen receptor (CAR) T cells engineered with an inducible cytokine to modulate the tumor stroma. Immunol Rev. 2014;257:83–90. doi: 10.1111/imr.12125. [PubMed] [CrossRef] []
72. Ahlert T, Sauerbrei W, Bastert G, Ruhland S, Bartik B, Simiantonaki N, Schumacher J, Häcker B, Schumacher M, Schirrmacher V. Tumor-cell number and viability as quality and efficacy parameters of autologous virus-modified cancer vaccines in patients with breast or ovarian cancer. J Clin Oncol. 1997;15:1354–1366. doi: 10.1200/JCO.1997.15.4.1354. [PubMed] [CrossRef] []
73. Schirrmacher V. Fifty years of clinical application of Newcastle disease virus: Time to celebrate. Biomedicines. 2016;4:E16. doi: 10.3390/biomedicines4030016. [PMC free article] [PubMed] [CrossRef] []
74. Ch’ng WC, Stanbridge EJ, Yusoff K, Shafee N. The oncolytic activity of Newcastle disease virus in clear cell carcinoma cells in normoxic and hypoxic conditions: The interplay between VHL and interferon beta signaling. J Interferon Cytokine Res. 2013;33:346–354. doi: 10.1089/jir.2012.0095. [PMC free article] [PubMed] [CrossRef] []
75. Schirrmacher V. Oncolytic Newcastle disease virus as a prospective anti-cancer therapy. A biological agent with potential to break therapy resistance. Exp Opon Biol Ther. 2015;15:1–15. [PubMed] []
76. Steiner HH, Bonsanto MM, Beckhove P, Brysch M, Geletneky K, Ahmadi R, Schuele-Freyer R, Kremer P, Ranaie G, Matejic D, et al. Antitumor vaccination of patients with glioblastoma multiforme: A pilot study to assess feasibility, safety, and clinical benefit. J Clin Oncol. 2004;22:4272–4281. doi: 10.1200/JCO.2004.09.038. [PubMed] [CrossRef] []
77. Schulze T, Kemmner W, Weitz J, Wernecke KD, Schirrmacher V, Schlag PM. Efficiency of adjuvant active specific immunization with Newcastle disease virus modified tumor cells in colorectal cancer patients following resection of liver metastases: Results of a prospective randomized trial. Cancer Immunol Immunother. 2009;58:61–69. doi: 10.1007/s00262-008-0526-1. [PubMed] [CrossRef] []
78. Schirrmacher V, Fournier P, Schlag P. Autologous tumor cell vaccines for post-operative active-specific immunotherapy of colorectal carcinoma: Long-term patient survival and mechanism of function. Expert Rev Vaccines. 2014;13:117–130. doi: 10.1586/14760584.2014.854169. [PubMed] [CrossRef] []
79. Schirrmacher V, Lorenzen D, Van Gool SW, Stuecker W. A new strategy of cancer immunotherapy combining hyper-thermia/oncolytic virus pretreatment with specific autologous anti-tumor vaccination - A review. Austin Oncol Case Rep. 2017;2:1006. []
80. Yagawa Y, Tanigawa K, Kobayashi Y, Yamamoto M. Cancer immunity and therapy using hyperthermia with immunotherapy, radiotherapy, chemotherapy, and surgery. J Cancer Metastasis Treat. 2017;3:218–230. doi: 10.20517/2394-4722.2017.35. [CrossRef] []
81. Desjardins A, Gromeier M, Herndon JE, Beaubier N, II, Bolognesi DP, Friedman AH, Friedman HS, McSherry F, Muscat AM, Nair S, et al. Recurrent glioblastoma treated with recombinant poliovirus. N Engl J Med. 2018;379:150–161. doi: 10.1056/NEJMoa1716435. [PMC free article] [PubMed] [CrossRef] []
82. VanGool SW, Makalowsky J, Feyen O, Prix L, Schirrmacher V, Stuecker W. The induction of immunogenic cell death (ICD) during maintenance chemotherapy and subsequent multimodal immunotherapy for glioblastoma (GBM) Austin Oncol Case Rep. 2018;3:1010. []
83. Watanabe D, Goshima F. Oncolytic Virotherapy by HSV. Adv Exp Med Biol. 2018;1045:63–84. doi: 10.1007/978-981-10-7230-7_4. [PubMed] [CrossRef] []
84. Russell SJ. RNA viruses as virotherapy agents. Cancer Gene Ther. 2002;9:961–966. doi: 10.1038/sj.cgt.7700535. [PubMed] [CrossRef] []
85. Cassel WA, Garrett RE. Newcastle disease virus as an anti-neoplastic agent. Cancer. 1965;18:863–868. doi: 10.1002/1097-0142(196507)18:7<863::AID-CNCR2820180714>3.0.CO;2-V. [PubMed] [CrossRef] []
86. Kroemer G, Galluzzi L, Kepp O, Zitvogel L. Immunogenic cell death in cancer therapy. Annu Rev Immunol. 2013;31:51–72. doi: 10.1146/annurev-immunol-032712-100008. [PubMed] [CrossRef] []
87. Koks CA, Garg AD, Ehrhardt M, Riva M, Vandenberk L, Boon L, De Vleeschouwer S, Agostinis P, Graf N, Van Gool SW. Newcastle disease virotherapy induces long-term survival and tumor-specific immune memory in orthotopic glioma through the induction of immunogenic cell death. Int J Cancer. 2015;136:E313–E325. doi: 10.1002/ijc.29202. [PubMed] [CrossRef] []
88. Jarahian M, Watzl C, Fournier P, Arnold A, Djandji D, Zahedi S, Cerwenka A, Paschen A, Schirrmacher V, Momburg F. Activation of natural killer cells by newcastle disease virus hemagglutinin-neuraminidase. J Virol. 2009;83:8108–8121. doi: 10.1128/JVI.00211-09. [PMC free article] [PubMed] [CrossRef] []
89. Zamarin D, Holmgaard RB, Subudhi SK, Park JS, Mansour M, Palese P, Merghoub T, Wolchok JD, Allison JP. Localized oncolytic virotherapy overcomes systemic tumor resistance to immune checkpoint blockade immunotherapy. Sci Transl Med. 2014;6:226ra32. doi: 10.1126/scitranslmed.3008095. [PMC free article] [PubMed] [CrossRef] []
90. Sampath P, Li J, Hou W, Chen H, Bartlett DL, Thorne SH. Crosstalk between immune cell and oncolytic vaccinia therapy enhances tumor trafficking and antitumor effects. Mol Ther. 2013;21:620–628. doi: 10.1038/mt.2012.257. [PMC free article] [PubMed] [CrossRef] []
91. Fournier P, Schirrmacher V. Bispecific antibodies and trispecific immunocytokines for targeting the immune system against cancer: Preparing for the future. BioDrugs. 2013;27:35–53. doi: 10.1007/s40259-012-0008-z. [PubMed] [CrossRef] []
92. Ribas A, Dummer R, Puzanov I, VanderWalde A, Andtbacka RH, Michielin O, Olszanski AJ, Malvehy J, Cebon J, Fernandez E, et al. Oncolytic virotherapy promotes intratumoral T cell infiltration and improves anti-PD1 immunotherapy. Cell. 2017;170:1109–1119.e10. doi: 10.1016/j.cell.2017.08.027. [PubMed] [CrossRef] []
93. Harrington KJ, Puzanov I, Hecht JR, Hodi FS, Szabo Z, Murugappan S, Kaufman HL. Clinical development of talimogene laherparepvec (T-VEC): A modified herpes simplex virus type-1-derived oncolytic immunotherapy. Expert Rev Anticancer Ther. 2015;15:1389–1403. doi: 10.1586/14737140.2015.1115725. [PubMed] [CrossRef] []
94. Stojdl DF, Lichty B, Knowles S, Marius R, Atkins H, Sonenberg N, Bell JC. Exploiting tumor-specific defects in the interferon pathway with a previously unknown oncolytic virus. Nat Med. 2000;6:821–825. doi: 10.1038/77558. [PubMed] [CrossRef] []
95. Fournier P, Wilden H, Schirrmacher V. Importance of retinoic acid-inducible gene I and of receptor for type I interferon for cellular resistance to infection by Newcastle disease virus. Int J Oncol. 2012;40:287–298. [PubMed] []
96. Schirrmacher V. Signaling through RIG-I and type I interferon receptor: Immune activation by Newcastle disease virus in man versus immune evasion by Ebola virus (Review) Int J Mol Med. 2015;36:3–10. doi: 10.3892/ijmm.2015.2213. [PubMed] [CrossRef] []
97. Ivashkiv LB, Donlin LT. Regulation of type I interferon responses. Nat Rev Immunol. 2014;14:36–49. doi: 10.1038/nri3581. [PMC free article] [PubMed] [CrossRef] []
98. Zaslavsky E, Hershberg U, Seto J, Pham AM, Marquez S, Duke JL, Wetmur JG, Tenoever BR, Sealfon SC, Kleinstein SH. Antiviral response dictated by choreographed cascade of transcription factors. J Immunol. 2010;184:2908–2917. doi: 10.4049/jimmunol.0903453. [PMC free article] [PubMed] [CrossRef] []
99. Tough DF. Type I interferon as a link between innate and adaptive immunity through dendritic cell stimulation. Leuk Lymphoma. 2004;45:257–264. doi: 10.1080/1042819031000149368. [PubMed] [CrossRef] []
100. Lattanzi L, Rozera C, Marescotti D, D'Agostino G, Santodonato L, Cellini S, Belardelli F, Gavioli R, Ferrantini M. IFN-α boosts epitope cross-presentation by dendritic cells via modulation of proteasome activity. Immunobiology. 2011;216:537–547. doi: 10.1016/j.imbio.2010.10.003. [PubMed] [CrossRef] []
101. Bommareddy PK, Shettigar M, Kaufman HL. Integrating oncolytic viruses in combination cancer immunotherapy. Nat Rev Immunol. 2018;18:498–513. doi: 10.1038/s41577-018-0014-6. [PubMed] [CrossRef] []
102. Collins JM, Redman JM, Gulley JL. Combining vaccines and immune checkpoint inhibitors to prime, expand, and facilitate effective tumor immunotherapy. Expert Rev Vaccines. 2018;17:697–705. doi: 10.1080/14760584.2018.1506332. [PubMed] [CrossRef] []
103. van Willigen WW, Bloemendal M, Gerritsen WR, Schreibelt G, de Vries IJ, Bol KF. Dendritic cell cancer therapy: Vaccinating the right patient at the right time. Front Immunol. 2018;9:2265. doi: 10.3389/fimmu.2018.02265. [PMC free article] [PubMed] [CrossRef] []
104. Abbas KA, Lichtman AH, Pillai S, editors. Cellular and Molecular Immunology. 6th Edition. Saunders Elsevier; Oxford: 2010. p. 261. []

Articles from International Journal of Oncology are provided here courtesy of Spandidos Publications

Plaats een reactie ...

Reageer op "Behandelen van kanker verschuift steeds meer van chemotherapie naar biologische behandelingen, gerichte therapie waaronder immuuntherapie met gemoduleerde virussen die de minste bijwerkingen geven"


Gerelateerde artikelen
 

Gerelateerde artikelen

6 nieuwe doorbraken in de >> 90 procent van mensen met >> Antibiotica binnen een maand >> Anti-PD medicijnen zoals nivolumab, >> Bacterien in uitzaaiingen >> Behandelen van kanker verschuift >> Biomarkers zoals PD-L1, CD163+ >> Bloedtest, uitgevoerd op in >> CHRISPR-CAS9 infuus blijkt >> De biologische processen waarom >>