Phase Ia clinical trial of adoptively transferring peripheral blood-derived cytotoxic T lymphocytes targeting individual neo-antigens to treat patients with advanced solid tumor.

Abstract

e14025 Background: Adoptive transfer of tumor infiltrating lymphocytes (TILs) targeting neo-antigens mediates complete and durable regression of solid tumor. However, the limited availability of fresh tumor samples hinders the application of TILs treatment. Based on neo-antigen specific T cells occurring in the circulation, we carried out a phase Ia clinical trial that adoptive transfer of peripheral blood-derived cytotoxic T lymphocytes (CTLs) targeting individual neo-antigens administrated patients with advanced solid tumor. Methods: This phase Ia clinical trial (NCT02959905) is designed to test the safety and objective response of CTL targeting individual neo-antigens treatment. Patients underwent apheresis on day -25, 0, 25, 50, 85 and 110, then CD8+T cells were isolated from peripheral blood and co-cultured with autologous dendritic cells pulsed with neo-antigens, which generated the infused CTLs targeting neo-antigens. On day 0, 25, 50, 85, 110 and 135, patients received CTLs respectively, which were prepared prior to 25 days. Patients received evaluations on day 55 and 140, and were followed up from day 150 for 32 weeks. The survival of the infused CTLs was analyzed according to the sequence of CDR3 regions of the T-cell receptor. Results: Until October 16th, 2018, a total of 10 patients were enrolled, 9 patients were infused 0.35-4×108 of CTLs for 1-6 times in this trial, in which 8 cases were metastatic melanoma and 1 case was colorectal cancer. Of the 10 participants who were enrolled, 7 participants had been evaluated, in which 1 case was evaluated as partial response (PR), 1 case was evaluated as iPR (evaluated as PR based on iRECIST), 3 cases were evaluated as stable disease (SD), 2 case were evaluated as progression of disease (PD), the objective reaction rate was 28.57%, and the disease control rate was 71.4%. All the subjects had safe tolerance, and the highest grade of adverse events related to adoptive cell transfer was grade 2. Neo-antigen specific CTLs persistently occurred in peripheral blood of 2 participants with PR or iPR for 140 days. Conclusions: Adoptively transferring peripheral blood-derived cytotoxic T lymphocytes targeting individual neo-antigens to treat patients with advanced solid tumor was safe under our current dose and preliminarily efficient. Clinical trial information: NCT02959905.