A Pilot Trial Of Multiple-Tsa-Specific Adoptive Immune Cell (Maic) As Adjuvant Therapy In Gastrointestinal Cancer.

e15013 Background: Given the heterogeneity of tumors, more tumor antigens need to be covered for better efficacy in oncologic immunotherapy. We conducted a pilot clinical trial to evaluate the safety and efficacy of adoptive immune cell therapy targeting multiple tumor specific antigens in individual patients. Methods: A total of 10 patients bearing resectable gastrointestinal tumor are going to be recruited in the study. The tumor-specific antigens of each patient were identified by RNA sequencing of the surgical tumor tissue. And then the antigenic peptides were synthesized and adapted to produce the multiple-TSA-specific adoptive immune cells (MAIC), including dendritic cell (DC) and cytotoxic T lymphocyte (CTL). 1st dose of MAICs injected during the 2nd or 3rd week after surgery; three doses of MAICs administered at 3-week intervals. Results: Currently, 4 patients have been enrolled, as shown in Table. The first enrolled patient, P01, underwent adjuvant MAIC therapy and have no progression nearly 9 months. P02, P03 and P04 developed new lesions about 3 months after the 1st surgery. After the 2nd surgery, tumor antigens were modified and MAIC targeting new antigens were given for adjuvant therapy. Up to now, there were no death events with survival months from 6.57 to 9.10. Safety evaluation showed that no irAE occurred in 4 patients. Intriguingly, antigenic drift was observed in patient P02.The top 3 antigens were shift from GPC3, AFP and GAGE10 to MAGEA1, GPC3 and CTAG2. And the mutation profile of tumors revealed totally different tumor clones with no shared SNV mutation between two surgery lesions at all. Through TCR sequencing, we found new T cell clones introduced by MAICs persisted in peripheral blood (sum ratio variated from 6.47% to 9.68%). Among them, specific T cell clones were identified targeting four antigens, including GPC3, AFP, TERT and MAGEA1. Among them, TERT-specific T cell clones shew highest expansion ratio, from 0.63±0.17% in PBMC to 7.85±3.10% in CTL. Conclusions: Treatment with MAICs have be proved safety in resectable gastrointestinal cancer. And all together four-antigen-specific T cell clones elevated apparently in peripheral blood after the 1st infusion of MAIC, reflecting the advantage of MAIC at renewable antigenic targets. [Table: see text]