Helpt u ons aan 500 donateurs?

19 mei 2018: lees ook dit artikel: 

https://kanker-actueel.nl/ivo-visser-uitbehandeld-voor-zeldzame-vorm-van-lymfklierkanker-komt-alsnog-in-total-remissie-kankervrij-met-t-car-cel-immuuntherapie.html

31 augustus 2017: Lees ook dit artikel: 

https://kanker-actueel.nl/NL/immuuntherapie-met-car-t-cell-therapy-tisagenlecleucel-kymriah-goedgekeurd-door-fda-voor-gebruik-bij-kinderen-en-jong-volwassenen-met-vorm-van-acute-lymfatische-leukemie-all.html

7 november 2015: lees het verhaal van Layla, een baby nog geen jaar oud die via immuuntherapie met T-cellen van een donor, T-cell enginering geheten, toegepast vlak voordat ze zou sterven, alsnog in een totale remissie kwam en nu al ruim dire maanden kankervrij is. Het verhaal van Layla met All - Acute Lymfatische Leukemie is wereldwijd overal gepubliceerd maar lees hier hoe de Volkskrant en Nature erover schrijven: 

https://kanker-actueel.nl/NL/layla-een-baby-met-ongeneeslijke-vorm-van-all-acute-lymfatische-leukemie-lijkt-alsnog-te-genezen-door-immuuntherapie-met-t-cellen-van-een-donor-via-t-cell-enginering-therapie.html

15 september 2017: Bron: ESMO 2017

Wanneer longkankerpatienten met operabele niet-klein-cellige longkanker na een succesvolle operatie aanvullend naast chemo immuuntherapie krijgen met een combinatie van dendritische celtherapie plus gemoduleerde T-cellen dan hebben zij 25 procent grotere kans de 5 jaar te overleven en uiteindelijk te genezen dan met alleen chemotherapie. 

Aan de studie deden totaal 103 patiënten met operabele longkanker mee. Groep A (N = 51 patiënten) kreeg chemo plus immuuntherapie met dendritische celtherapie plus gemoduleerde T-cellen. Groep B (N = 52 patiënten) kreeg alleen chemo.

De 2-jaars overall overleving (OS) waren respectievelijk in groep A (chemo plus immuuntherapie) 96,0 procent vs 64,7 procent in groep B (alleen chemo) en 5-jaars overall overleving (OS) 69.4% versus 45.1% in groep B.

Ook het verschil in progressievrije ziekte was veel beter met immuuntherapie dan zonder: op respectievelijk 2 en 5 jaars meting: 70.0% (groep A) en 43,1% (groep B) en 57,9% (groep A) en 31.4% (groep B), respectievelijk.

Dendritische celtherapie met gemoduleerde T-cellen

In dit studierapport: Synergistic Effect of Dendritic Cell Vaccine with Immune Modulating Chemo Drugs wordt beschreven hoe dendritische celtheprie met gemoduleerde T-cellen werkt en is volledig gratis te bekijken.

Hier het abstract van de studie bij longkankerpatiënten: Phase III randomized controlled trial of adjuvant chemoimmunotherapy in patients with resected primary lung cancer waarvan de eindresultaten op ESMO 2017 werden gepresenteerd.

Daaronder het abstract met referentielijst van deze studie: Role of Cell Based Approaches in Cancer Immunotherapy een aanvulling op de andere studie: Synergistic Effect of Dendritic Cell Vaccine with Immune Modulating Chemo Drugs

Non-small-cell lung cancer patients benefitedfrom adoptive cellular immunotherapy asanadjuvant to surgery. Immunological analysis of cell surface markers indicated cytotoxic Tcells were essential for a favorable chemo immunotherapy outcome.

Source: ESMO 2017:

Phase III randomized controlled trial of adjuvant chemoimmunotherapy in patients with resected primary lung cancer
H. Kimura1, Y. Matsui2, T. Nakajima3, T. Iizasa4, A. Ishikawa3 1Thoracic Surgery, Saiseikai Narashino Hospital, Narashino City, Chiba, Japan, 2Thoracic Surgery, Chiba Cancer Center, Nitona-cho-, Chiba, Japan, 3General Thoracic Surgery, Graduate School of Medicine, Chiba Univercity, Chu-o-ku, Chiba, Japan, 4Thoracic Surgery, Chiba Cancer Center, Chu-o-ku, Chiba, Japan

Background:
Adoptive cellar immunotherapy is notwidely approvedasa treatment option for cancer treatment.The preliminary results from our phase III, randomized controlled trial (RCT) of adjuvant chemoimmunotherapyfor lung cancer indicated significant advantages in patients receiving immunotherapy. Here we report the final results and long-term analysis of this RCT.

Methods:
Ahundred and three postsurgical non-small-cell lung cancer patients were randomly designated to receive either chemoimmunotherapy(group A, immunotherapyarm, n¼51)or chemotherapy (group B, control arm, n¼52). The immunotherapyconsisted of adoptive transfer of autologous activated killer Tcells anddendritic cells obtained from regionallymph nodes of the patients.

Results:
The 2- and 5-year overall survival (OS) rates were 96    0% and 69.4% in group Aand 64    7% and45.1% in group B, respectively. The hazard ratio (HR)was 0.451 (0.2350.807) by multivariate analysis. The 2- and 5-year recurrence-free survival rates were 70.0% and 57    9% in group Aand 43.1% and 31.4% in group B, respectively.P valuesof Log-rank test between groups were 0.0059. Subgroup analysis for the OS between treatment groups indicated males (HR, 0    474), adenocarcinoma patients(HR, 0    479), stage III cancer patients (HR, 0    399), and those who did not receive preoperative chemotherapy (HR, 0    483) had lower HRs than those in the other groups. Immunological analysis ofcellsurface markersin regional lymph nodesof subjects receiving immunotherapy indicated that the CD8þ/CD4þT-cell ratio was elevatedin survivors.

Conclusions:
Non-small-cell lung cancer patients benefitedfrom adoptive cellular immunotherapy asanadjuvant to surgery. Immunological analysis of cell surface markers indicated cytotoxic Tcells were essential for a favorable chemoimmunotherapy outcome. Clinical trial identification: The University Hospital Medical Information Network in Japan (UMIN:000007525). Legal entity responsible for the study: Chiba Cancer Center, Japan Funding: None Disclosure: All authors have declared no conflictsof interest.

Tangible benefits from DC vaccine can be realized by employing multifaceted approach including chemotherapy.

Synergistic Effect of Dendritic Cell Vaccine with Immune Modulating Chemo Drugs Anjum Mahmood1, Seetharaman Rajasekar2, Chandan Bora3 and Shiva Sreenath Andrali4* 1,2,3North American Biomedical Research Center, Brighton Estates, Cayon, St Kitts and Nevis, West Indies; 4North American Biomedical Research Center, 1927 Zonal Ave, Los Angeles, California-90033 research@nabrc.org*; Phone: 323-223-1927; Fax: 323-223-1940 ______________________________________________________________________________________________ Abstract Dendritic cells (DCs) have been tested for cancer immunotherapy over the past two decades in different clinical trials. During this period, efforts were put forth to optimize different parameters influencing the anti-tumor efficacy of ex-vivo generated DCs including maturation stimuli, antigen source, route of vaccine administration and adjuvant usage. In a recent paradigm shift, combinatorial therapy has emerged as possible answer to improve the efficacy of DC vaccines. Specifically, chemotherapy is reported to be associated with synergistic effects with DCs by altering the innate and adaptive arms of immune system. Chemotherapeutic drugs promote the molecular rearrangement on apoptotic tumor cells rendering them to be recognized by phagocytic DCs. The phagocytosis of immunogenic tumor cells results in maturation of DCs leading to an effective antitumor response. While the tumor suppressive microenvironment is subverted, the actions of chemo drugs also stimulate the immune effector cells either directly or indirectly by causing the release of cytokines. Here, we reviewed the assessment of the clinical development in DC vaccine trials and focused on combinatorial approaches using chemo drugs while understanding molecular mechanism underlying the interactions between anti-neoplastic drugs and immune cells. Synergistic Effect of Dendritic Cell Vaccine with Immune Modulating Chemo Drugs (PDF Download Available). Available from: https://www.researchgate.net/publication/278019740_Synergistic_Effect_of_Dendritic_Cell_Vaccine_with_Immune_Modulating_Chemo_Drugs [accessed Sep 15, 2017].

In light of current knowledge and advances in cancer immunotherapy we conclude that under optimal conditions, tangible benefits can be realized in cancer management.

Role of Cell Based Approaches in Cancer Immunotherapy
Anjum Mahmood1, Anjani Srivastava2, Shivangi Srivastava2, Hiteshree Pandya1, Neel Khokhani1, Divyang Patel1 and Rangnath Mishra3*
1GIOSTAR Research Pvt Ltd, India
2Global Institute of Stem Cell Therapy and Research, USA
3Department of Medicine, National Jewish Health, USA
Received:February 17, 2017 | Published: May 05, 2017
*Corresponding author: Rangnath Mishra, Department of Medicine, National Jewish Health, Denver, CO 80206, USA, Email:
Citation: Mahmood A, Srivastava A, Srivastava S, Pandya H, Khokhani N (2017) Role of Cell Based Approaches in Cancer Immunotherapy. J Stem Cell Res Ther 2(5): 00077. DOI: 10.15406/jsrt.2017.02.00077

Abstract

Immunotherapies hold the potential for cancer treatment since their mode of action is distinct to chemo and radiation therapy and largely depends on harnessing body’s own immune system. The major advantage associated with cancer immunotherapy is that cell responses are specific to tumor and with low or negligible toxicity. Preclinical and clinical studies have evidenced that modulation of immune system can subvert the immunosuppressive environment under progressive tumor conditions. The modulation can be brought into several ways including infusion of ex-vivo or in-vivo activated antigen presenting cells (dendritic cells), immune checkpoint antibodies, adoptive transfer of T cells, genetically modified T cells, cancer cell vaccines, stem cells, cytokines and others. In this review, we will keep the discussion focused to some of cell based approaches.

Recent advances in understanding the mechanism underlying tumor progression and role of immune system has laid the foundation of immunotherapy based interventions in clinical malignancies. By adopting unique immunotherapeutic approach specific to diseased condition and optimal conditions of delivery significant level of benefits can be expected. Further, exploration of new targeted strategies is also required to extend scope of application and avoid unwanted adverse events in patients. The targeting of other identified DC cell surface receptors like mannose receptor (MR), CIRE, DC-SIGN, DCIR, LSECtin, L-SIGN, Langerin, Dectin, DNGR-1, MICL, MGL CLEC2, CLEC12B, LOX-1, BDCA-2, DEC205, scavenger receptor, DC-ASGPR, FIRE, DC-STAMP and Toll-like receptors (TLRs) will definitely open the new dimensions in in-vivo DC based approaches [5]. Further, targeting of cancer stem cells (CSCs) via DCs will also improve specificity of anti-tumor activity. Similarly, role of MSC derived exosomes in delivery of therapeutic agents is also currently under investigation in several studies. Exosome-mediated delivery of tumor suppressor miRNAs and targeting of growth-regulatory pathways, such as the Wnt and Hedgehog pathways, as well as angiogenic pathways, such as the VEGF and kinase pathways, could be novel strategies to monitor tumor growth. In light of current knowledge and advances in cancer immunotherapy we conclude that under optimal conditions, tangible benefits can be realized in cancer management.

References

  1. Mahmood A, Rajasekar S, Bora C, Andrali SS (2015) Synergistic Effect of dendritic cell vaccine with immune modulating chemo drugs. Journal of Academia and Industrial Research 3(12): 590-597.
  2. O'Neill DW, Bhardwaj N (2005) Differentiation of peripheral blood monocytes into dendritic cells. Curr Protoc Immunol Chapter 22, Unit 22F, 4.
  3. Banchereau J, Palucka AK, Dhodapkar M, Taquet N, Rolland A, et al. (2001) Immune and clinical responses in patients with metastatic melanoma to CD34+ progenitor-derived dendritic cell vaccine. Cancer Res 61(17): 6451-6458.
  4. Turnis ME, Rooney CM (2010) Enhancement of dendritic cells as vaccines for cancer. Immunotherapy 2(6): 847-862.
  5. Higano CS, Schellhammer PF, Small EJ, Burch PA, Nemunaitis J, et al. (2009) Integrated data from 2 randomized, double-blind, placebo-controlled, phase 3 trials of active cellular immunotherapy with sipuleucel-T in advanced prostate cancer. Cancer 115(16): 3670-3679.
  6. Schuler PJ, Harasymczuk M, Visus C, Deleo A, Trivedi S, et al. (2014) Phase I dendritic cell p53 peptide vaccine for head and neck cancer. Clin Cancer Res20(9): 2433-2444.
  7. Coosemans A, Vanderstraeten A, Tuyaerts S, Verschuere T, Moerman P, et al. (2013) Wilms’ Tumor Gene 1 (WT1)-loaded dendritic cell imunotherapy in patients with uterine tumors: a phase I/II clinical trial. Anticancer Res33(12): 5495-5500.
  8. Hildenbrand B, Sauer B, Kalis O, Stoll C, Freudenberg MA, et al. (2007) Immunotherapy of patients with hormone-refractory prostate carcinoma pre-treated with interferon-gamma and vaccinated with autologous PSA-peptide loaded dendritic cells-a pilot study. Prostate 67(5): 500-508.
  9. Sharma A, Koldovsky U, Xu S, Mick R, Roses R, et al. (2012) HER-2 pulsed dendritic cell vaccine can eliminate HER-2 expression and impact ductal carcinoma in situ. Cancer 118(17): 4354-4362.
  10. Lee D, Kochenderfer J, Stetler-Stevenson M, Cui Y, Delbrook C, et al. (2014) T cells expressing CD19 chimeric antigen receptors for acute lymphoblastic leukaemia in children and young adults: a phase 1 dose-escalation trial. Lancet 385(9967): 517-528.
  11. Gardner R, Jensen M (2014) CD19CAR T cells: from humble beginnings to cancer immunotherapy’s poster child. Cancer J 20: 107-111.
  12. Tasian SK, Gardner RA (2015) CD19-redirected chimeric antigen receptor-modified T cells: a promising immunotherapy for children and adults with B-cell acute lymphoblastic leukemia (ALL). Ther Adv Hematol 6(5): 228-241.
  13. Whilding LM, Maher J (2015) ErbB-targeted CAR T-cell immunotherapy of cancer. Immunotherapy 7(3): 229-241.
  14. Scholl S, Beuzeboc P, Pouillart P (2001) Targeting HER2 in other tumor types. Annals of Oncology 12(Suppl 1): S81-S87
  15. Ahmed N, Brawley VS, Hegde M, Robertson C, Ghazi A, et al. (2015) Human epidermal growth factor receptor 2 (HER2)-specific chimeric antigen receptor-modified T cells for the immunotherapy of HER2-positive sarcoma. J Clin Oncol 33(15): 1688-1696.
  16. Feng K, Guo Y, Dai H, Wang Y2, Li X, et al. (2016) Chimeric antigen receptor-modified T cells for the immunotherapy of patients with EGFR-expressing advanced relapsed/refractory non-small cell lung cancer. Science China Life Sciences 59(5): 468-479.
  17. Almåsbak H, Aarvak T, Vemuri MC (2016) CAR T cell therapy: A game changer in cancer treatment. Journal of Immunology Research 2016: 10.
  18. Bakker AB, Schreurs MW, de Boer AJ, Kawakami Y, Rosenberg SA, et al. (1994) Melanocyte lineage-specific antigen gp100 is recognized by melanoma-derived tumor-infiltrating lymphocytes. J Exp Med 179(3): 1005-1009.
  19. Engelhard VH, Bullock TN, Colella TA, Sheasley SL, Mullins DW (2002) Antigens derived from melanocyte differentiation proteins: self-tolerance, autoimmunity, and use for cancer immunotherapy. Immunol Rev 188: 136-146.
  20. Robbins PE, el-Gamil M, Kawakami Y, Stevens E, Yannelli JR, et al. (1994) Recognition of tyrosinase by tumor-infiltrating lymphocytes from a patient responding to immunotherapy. Cancer Res 54(12): 3124-3126.
  21. Romero P, Gervois N, Schneider J, Escobar P, Valmori D, et al. (1997) Cytolytic T lymphocyte recognition of the immunodominant HLA-A*0201-restricted Melan-A/MART-1 antigenic peptide in melanoma. J Immunol 159(5): 2366-2374.
  22. Chen YT, Gure AO, Tsang S, Stockert E, Jager E, et al. (1998) Identification of multiple cancer/testis antigens by allogeneic antibody screening of a melanoma cell line library. Proc Natl Acad Sci USA 95(12): 6919-6923.
  23. Scanlan MJ, Gure AO, Jungbluth AA, Old LJ, Chen YT (2002) Cancer/testis antigens: an expanding family of targets for cancer immunotherapy. Immunolog Rev 188: 22-32.
  24. Rosenberg, SA, Packard BS, Aebersold PM, Solomon D, Topalian SL, et al. (1988) Use of Tumor-Infiltrating Lymphocytes and Interleukin-2 in the Immunotherapy of Patients with Metastatic Melanoma. N Engl J Med 319(25): 1676-1680.
  25. Rosenberg, SA, Yang JC, Sherry RM, Kammula US, Hughes MS, et al. (2011) Durable complete responses in heavily pretreated patients with metastatic melanoma using T cell transfer immunotherapy. Clin Cancer Res 17(13): 4550-4557.
  26. Gotherstrom C (2007) Immuno- modulation by multipotent mesenchymal stromalcells. Transplantation 84(1 Suppl): S35-S37.
  27. Loebinger MR, Janes SM (2010) Stem cells as vectors for antitumour therapy. Thorax 65(4): 362-369.
  28. Menon LG, Picinich S, Koneru R, Gao H, Lin SY, et al. (2007) Differential gene expression associated with migration of mesenchymal stem cells to conditioned medium from tumor cells or bone marrow cells. Stem Cells 25: 520-528.
  29. Ringden O, Uzunel M, Rasmusson I, Remberger M, Sundberg B, et al. (2006) Mesenchymal stemcells for treatment of therapy-resistant graft- versus-host disease. Transplantation 81(10): 1390-1397.
  30. Studeny M, Marini FC, Champlin RE, Zompetta C, Fidler IJ, et al. (2002) Bone marrow-derived mesenchymal stem cells as vehicles for interferon-beta delivery into tumors. Cancer Res 62(13): 3603-3608.
  31. Sasportas LS, Kasmieh R, Wakimoto H, Hingtgen S, van de Water JA, et al. (2009) Assessment of therapeutic efficacy and fate of engineered human mesenchymal stem cells for cancer therapy. Proc Natl Acad Sci USA 106(12) 4822-4827.
  32. Eliopoulos N, Francois M, Boivin MN, Martineau D, Galipeau J (2008) Neo-organoid of marrow mesenchymal stromal cells secreting interleukin-12 for breast cancer therapy. Cancer Res 68(12): 4810-4818.
  33. Xin H, Sun R, Kanehira M, Takahata T, Itoh J, et al. (2009) Intratracheal delivery of CX3CL1-expressing mesenchymal stem cells to multiple lung tumors. Mol Med 15(9-10): 321-327.
  34. Uchibori R, Okada T, Ito T, Urabe M, Mizukami H, et al. (2009) Retroviral vector-producing mesenchymal stem cells for targeted suicide cancer gene therapy. J Gene Med 11(5): 373-381.
  35. Gu C, Li S, Tokuyama T, Yokota N, Namba H (2010) Therapeutic effect of genetically engineered mesenchymal stem cells in rat experimental leptomeningeal glioma model. Cancer Lett 291(2): 256-262.

recidief, ziekteprogressie, anti-PD medicijnen, immuuntherapie, overall overleving, progressievrije tijd, niet-kleincellige longkanker, dendritische celtherapie, gemoduleerde T-cellen


Plaats een reactie ...

Reageer op "Longkanker: Dendritische celtherapie plus gemoduleerde T-cellen naast chemo geeft 25 procent betere mediane overall overleving op 5 jaar bij operabele niet-kleincellige longkanker"


Gerelateerde artikelen
 

Gerelateerde artikelen

CD19 Fast-CAR-T-cel therapie >> CAR-T celtherapie brengt binnen >> CAR-T celtherapie is zeer >> Immuuntherapie met gemanipuleerde >> Immuuntherapie met gemanipuleerde >> Dendritische celtherapie met >> Longkanker: Dendritische celtherapie >> Immuuntherapie met TIL - tumor >> Immuuntherapie met CAR T-Cell >> Immuuntherapie met T-car cells >>