Zie ook in gerelateerde artikelen.

Raadpleeg ook literatuurlijst niet-toxische middelen behandelingen specifiek bij eierstokkanker van arts-bioloog drs. Engelbert Valstar

29 juli 2021: Bron: Ther Adv Med Oncol. 2021; 13: 17588359211008399. Published online 2021 Apr 22.

In een recente overzichtstudie (april 2021) geven onderzoekers een historisch overzicht van verschillende vormen van immuuntherapie met de nadruk op gepersonaliseerde (CAR-) T-celtherapiën voor de behandeling van eierstokkanker in alle stadia, met ook aandacht voor dendritische celtherapie.

In onderstaande grafiek wordt in een schema weergegeven van wat er in de studie allemaal behandeld wordt en hoe met name gepersonaliseerde vormen van immuuntherapie worden gegeven:

An external file that holds a picture, illustration, etc.
Object name is 10.1177_17588359211008399-fig1.jpg

An external file that holds a picture, illustration, etc.
Object name is 10.1177_17588359211008399-fig1.jpg

General schematic for using DC vaccines and TIL-ACT for patients with overian cancer (OC).

A schematic is shown which describes the key steps in preparation of TIL-ACT for OC cancer therapy. The resected specimen and blood draw, generally via a leukapheresis procedure are taken from the patient. The resected specimen is divided into multiple tumor fragments that are individually grown in high-dose 6000 UI IL-2 for 7–14 days (pre-REP phase). For the ‘unselected’ TIL therapy (dashed line) the individual cultures are then moved to a rapid-expansion protocol (REP) in the presence of irradiated feeder lymphocytes, anti-CD3, and IL-2 before re-infusion into patients. The NeoAg-TIL therapy entails the sequencing of exomic or whole-genome DNA from tumor cells and healthy cells to call tumor-specific mutations. Corresponding minigenes or peptides encoding each mutated amino acid are synthesized and expressed in, or pulsed into, a patient’s autologous antigen-presenting cells (APCs) for presentation in the context of a patient’s HLA. The identification of individual mutations responsible for tumor recognition is possible with analysis of the T-cell activation marker, such as CD137 (CD8+ T cells), when they recognize their cognate target antigen.

In hun conclusie schrijven de onderzoekers wel dat er nog weinig echt goede studies hebben bewezen goede resultaten te geven voor immuuntherapie bij gevorderde eierstokkanker. Maar ook hier speelt het probleem dat immuuntherapie in heel veel studies pas wordt ingezet bij patiënten met vergevorderde kanker. Er zijn weinig studies die onderzoek doen naar de effectiviteit bij patiënten met weinig of geen tumorload bij de start van de immuuntherapie.

Het volledige studierapport is gratis in te zien of te downloaden. Klik op de titel.

2021; 13: 17588359211008399.

Published online 2021 Apr 22. doi: 10.1177/17588359211008399

PMCID: PMC8072818

PMID: 33995591

Cell therapies in ovarian cancer

Apostolos Sarivalasis, Matteo Morotti, Arthur Mulvey, Martina Imbimbo, and George Coukos

Author information Article notes Copyright and License information Disclaimer

This article has been corrected. See Ther Adv Med Oncol. 2021 June 17; 13: 17588359211028457.

Abstract

Epithelial ovarian cancer (EOC) is the most important cause of gynecological cancer-related mortality. Despite improvements in medical therapies, particularly with the incorporation of drugs targeting homologous recombination deficiency, EOC survival rates remain low. Adoptive cell therapy (ACT) is a personalized form of immunotherapy in which autologous lymphocytes are expanded, manipulated ex vivo and re-infused into patients to mediate cancer rejection. This highly promising novel approach with curative potential encompasses multiple strategies, including the adoptive transfer of tumor-infiltrating lymphocytes, natural killer cells, or engineered immune components such as chimeric antigen receptor (CAR) constructs and engineered T-cell receptors. Technical advances in genomics and immuno-engineering have made possible neoantigen-based ACT strategies, as well as CAR-T cells with increased cell persistence and intratumoral trafficking, which have the potential to broaden the opportunity for patients with EOC. Furthermore, dendritic cell-based immunotherapies have been tested in patients with EOC with modest but encouraging results, while the combination of DC-based vaccination as a priming modality for other cancer therapies has shown encouraging results. In this manuscript, we provide a clinically oriented historical overview of various forms of cell therapies for the treatment of EOC, with an emphasis on T-cell therapy.

Conclusions

Despite high rates of response to initial treatment, EOC has a high recurrence rate and has yet to show a significant response to available immunotherapeutic agents. Cell therapies have transformed the treatment paradigm for patients with hematologic malignancies; however, the translation of this success to the unmet need of EOC patients is ongoing. Cell-based therapies in EOC have been explored in early-phase studies from a few highly specialized centers, with modest clinical results, raising concerns for the future development of these potentially curative therapeutic approaches.

Previous experience with ACT-TIL has shown the feasibility of this complex approach in the setting with EOC. The incorporation of new technologies such as DNA sequencing, DNA synthesis, and genetic screening tools to identify individual patient-specific NeoAgs with high sensitivity, specificity, and at scale, might broaden the application of this type of treatment to a broader group of EOC patients in coming years. Vaccination strategies have, to date, mainly encompassed shared TAAs and have been met with limited success.

A better understanding of the T-cell biology (T-cell exhaustion) driven by the peculiar EOC TME will be a crucial step in developing ACT for these patients. It will drive advances in T-cell engineering and clinical trial design with combination therapies. The immunosuppressive TME needs to be tackled to improve CAR-T and TIL-ACT products’ activity and persistence, and immune-engineering innovative solutions are currently being developed. Similarly, as T-cell engineering technology is streamlined, it might gain a prominent role in combination with other strategies. We believe that a better understanding of these key biological questions, along with technological developments will be key to broadening the use of cell therapeutics and ultimately improve EOC patients’ clinical outcomes.

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Footnotes

Conflict of interest statement: Dr Coukos reports grants from Celgene, grants from Boehringer-Ingelheim, personal fees from Genentech, grants from Roche, personal fees from Roche, grants from BMS, personal fees from BMS, personal fees from AstraZeneca, grants from Iovance Therapeutics, grants from Kite Pharma, personal fees from NextCure, personal fees from Geneos Tx, and personal fees from Sanofi/Avensis outside the submitted work;Dr Coukos has patents in the domain of antibodies and vaccines targeting the tumor vasculature as well as technologies related to T-cell expansion and engineering for T-cell therapy. Dr Coukos holds patents around TEM1 antibodies and receives royalties from the University of Pennsylvania regarding technology licensed to Novartis.Dr Sarivalasis reports consultancy and advisory fees from Roche, Novartis, GSK, Tesaro, BMS, Celgene, BMS, AstraZeneca. Research grants from Roche. Travel fees from Roche, GSK, Tesaro, Clovis, AstraZeneca, MSD, Pfizer, Amgen, Celgene, Novartis.

Funding: The authors received no financial support for the research, authorship, and/or publication of this article.

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Contributor Information

Apostolos Sarivalasis, Department of Oncology, Lausanne University Hospital, University of Lausanne, Lausanne, Switzerland.

Matteo Morotti, Department of Oncology, Lausanne University Hospital, University of Lausanne, Lausanne, Switzerland. Ludwig Institute for Cancer Research, Lausanne Branch, University of Lausanne, Lausanne, Switzerland.

Arthur Mulvey, Department of Oncology, Lausanne University Hospital, University of Lausanne, Lausanne, Switzerland.

Martina Imbimbo, Department of Oncology, Lausanne University Hospital, University of Lausanne, Lausanne, Switzerland.

George Coukos, CHUV, Rue du Bugnon 46, Lausanne BH09-701, Switzerland.

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Articles from Therapeutic Advances in Medical Oncology are provided here courtesy of SAGE Publications

eierstokkanker, immuuntherapie, dendritische celtherapie, overzichtstudie, CAR-T celtherapie, anti-PD medicijnen, pembrolizumab, overall overleving, ziektevrije tijd