| Autor: |
Daniel Kallin, Marit M. van Buuren, Jessica Kohler, Jonathan McGee, C.M. Nijenhuis, Joost H. van den Berg, Dewi Harjanto, Paul J. Turcott, Janani Sridar, Divya Lenkala, Brian C. McCarthy, Richard B. Gaynor, Michael D. Nelson |
| Rok vydání: |
2020 |
| Předmět: |
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| Zdroj: |
Journal for ImmunoTherapy of Cancer, Vol 8, Iss Suppl 3 (2020) |
| Popis: |
Background Neoantigens are tumor-specific antigens that are important in the anti-tumor immune response. These antigens are not subject to central immune tolerance and are therefore potentially more immunogenic than tumor-associated antigens. NEO-STIM®, our propriety ex vivo induction process, was developed to generate T-cell products specific to these neoantigens from the peripheral blood of patient. Here, we present the results of a proof of concept, pre-clinical study with multiple successful process engineering runs generating a neoantigen-specific T-cell product (NEO-PTC-01) using leukaphereses from metastatic melanoma patients. These products contain specific T-cell responses targeting multiple neoantigens from each individual patient‘s tumor. Methods Patient-specific neoantigens were predicted using our RECON® bioinformatics platform. Predicted high-quality neoantigens were utilized in our ex vivo stimulation protocol, NEO-STIM, in the process engineering runs of NEO-PTC-01. NEO-STIM is used to prime, activate and expand memory and de novo T-cell responses from both the CD4+ and the CD8+ compartment. High throughput flow cytometric analysis was performed to characterize the specificity and functionality (cytokine production and cytolytic capacity) of the induced T-cell responses. Results Here we present the successful induction of 4–5 CD8+ and 4–7 CD4+ T-cell responses per patient, generated using peripheral blood mononuclear cells from multiple melanoma patients during these successful process engineering runs. We then extensively characterized these T-cell responses and demonstrate that these responses are functional, specific and have cytolytic capacity. Moreover, the induced T cells can recognize autologous tumor. Conclusions NEO-STIM is a novel platform that generates ex vivo T-cell responses to high-quality neoantigen targets. NEO-PTC-01, the neoantigen-specific T cell product generated from this process, is a potent adoptive cell therapy targeting multiple immunogenic neoantigens in patients with metastatic melanoma. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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