TUMOR-INFILTRATING LYMPHOCYTES EXPRESSING ANTI-PD-1 ANTIBODY EXHIBIT A PROMISING EFFICACY AND SURVIVAL BENEFIT IN PATIENTS WITH RECURRENT GLIOBLASTOMA MULTIFORME

Abstract Adoptive cell therapies utilizing autologous tumor-infiltrating lymphocytes (TIL) have been demonstrated to be safe and promising in anti-tumor activities; However, their efficiency was still low in treating glioblastoma multiforme (GBM) because of immunosuppression microenvironment. In this study, we proposed a new strategy to enhance the anti-tumor immune response by using modified TIL expressing anti-PD-1 antibody (anti-PD1-TIL), which could reverse immunosuppression in tumor microenviroment. From April 2017 to April 2018，a total of 8 patients with recurrent GBM were enrolled and received more than one cycles of anti-PD1-TIL immunotherapy after surgery and chemotherapy with a median follow-up of 20 months. The anti-PD1-TIL immunotherapy was well tolerated. Two patients suffered grade 1 and 2 adverse events, including fatigue, mucosal/cutaneous toxicities. The median overall survival time was 16.1（95% CL: 15.4–16.7）months. By iRANO criteria, one patient experienced a partial response (PR), and three patients experienced stable disease (SD) after anti-PD-1-TIL immunotherapy. Genomic analysis by whole exome sequencing revealed an enrichment of MUC12 mutation in responders (p< 0.01), and an enrichment of TMEM125 (p< 0.01) and HIST2H3A/C amplification (p< 0.05) associated with immunosuppressive signature in non-responders. Taken together, the anti-PD1-TIL immunotherapy is a safe and promising strategy with durable efficacy to treat patients with recurrent GBM. Clinicaltrials.gov identifier: NCT 03347097.