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Anne-Laure Joly, S. Berglund, E. L. Maître, A. Lukić, L. Notari, Ola B. Nilsson, G. Gafvelin, H. Grönlund
0 1. 11. 2022.

654 Personalised tumour-trained lymphocytes derived from regional lymph nodes for treatment of colorectal cancer

Background Adoptive T cell therapy as a treatment for solid tumours is gaining increasing interest. Cancer neoantigens as targets for such therapy is also gaining recognition. Personalised tumour trained lymphocytes (pTTL) is a novel autologous T cell therapy targeting patient-specific neoantigens. A phase I/ II First in Human (FIH) clinical trial of pTTL in Stage IV colorectal cancer (CRC) patients will be initiated in the near future. Methods pTTL is produced through in vitro expansion of T cells derived from regional lymph nodes (RLNs). The T cells derived from RLNs, nodes in anatomical proximity of the tumour, contain a pool of naive and antigen-experienced T cells enriched for tumour-antigen specificity. This enriched population is stimulated during pTTL production with an array of neoantigen epitopes individually designed using PIOR ® , an in house-developed software for neoantigen detec-tion and selection. Selected neoantigens are linked to paramag-netic particles using EpiTCer ® technology. The resulting EpiTCer ® particles are used to stimulate the RLN T cells via phagocytosis and presentation of the neoantigen epitopes by antigen-presenting cells. This process is HLA-independent. Each pTTL product is unique due to the personalised nature of cellular and molecular players (cancer characteristics, immune cell properties and neoantigens are specific to one single individual).

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