A First-in-Human, phase I/IIa trial of the novel T cell immunotherapy pTTL in patients with advanced colorectal cancer

Abstract Introduction T cell therapy targeting neoantigens is a promising new treatment approach for solid tumors. Neoantigens are altered and potentially immunogenic proteins resulting from genetic changes during tumorigenesis. Personalized tumor trained lymphocytes (pTTL) is a novel autologous neoantigen-directed T cell product produced from regional lymph nodes (RLN). A phase I/II First-in-Human clinical trial of pTTL in Stage IV colorectal cancer (CRC) patients is ongoing. Method pTTL is produced through in vitro expansion of T cells derived from tumor-adjacent RLNs. RLN T cells are stimulated with patient-specific neoantigens utilizing the proprietary EpiTCer® technology. Next generation sequencing data is obtained from tumor and normal tissue and analyzed with the bioinformatic software PIOR® to identify and select tumor-specific neoantigens. These are then produced and linked to EpiTCer® micro-particles, which are used for tumor-selective T cell expansion during pTTL manufacturing. In the ongoing Phase I/IIa trial, up to 16 adult patients with stage IV CRC will be treated with a single dose of pTTL following pre-conditioning with cyclophosphamide and fludarabine. RLN for pTTL production will be collected during standard-of-care surgery or study-specific surgery. The primary study endpoint is safety. Secondary outcomes include objective response, overall survival, and progression-free survival. Result The pTTL manufacturing process is robust, generating a high proportion of approved products. The products vary regarding T cell characteristics, including the CD4/CD8 ratio. pTTL contains a significant proportion of memory T cells. Discussion Early results indicate a satisfactory safety profile: only low-grade adverse reactions to pTTL have been reported for the first treated patients.