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153 NEO-PTC-01 (BNT-221), an autologous neoantigen-specific T-cell product for adoptive cell therapy of metastatic melanoma
  1. Divya Lenkala1,
  2. Jessica Kohler1,
  3. Brian McCarthy1,
  4. Michael Nelson1,
  5. Jonathan McGee1,
  6. Daniel Kallin1,
  7. Janani Sridar1,
  8. Paul Turcott1,
  9. Dewi Harjanto1,
  10. Cynthia Nijenhuis2,
  11. Joost Van Den Berg2,
  12. Richard Gaynor1 and
  13. Marit Van Buuren1
  1. 1BioNTech US Inc., Cambridge, MA, USA
  2. 2Netherlands Cancer Institute, Cambridge, MA, USA


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.

This is an open access article distributed in accordance with the Creative Commons Attribution 4.0 Unported (CC BY 4.0) license, which permits others to copy, redistribute, remix, transform and build upon this work for any purpose, provided the original work is properly cited, a link to the licence is given, and indication of whether changes were made. See:

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