P1.04-34 Study on Treatment of Stage IV Solid Tumors with Mutant Neoantigen Specific T Cells

As an important tumor immunotherapy, the specificity and efficiency of PD1 inhibitor is not yet satisfactory. The treatment of solid tumor with mutant neoantigen specific T (Nas-T) cells developed in this study is an adoptive cell therapy which is specific for each patient. The aim is to explore the difference in safety and efficacy between Nas-T cells and PD1 inhibitors, and to evaluate the charateristic of immune repertoire (IR) as predictive biomarker. A total number of 11 patients with advanced solid tumors who failed after multiline treatments were recruited. They were treated with Nas-T cells, PD1 inhibitors and BSC; other 11 patients were treated with PD1 inhibitors and BSC as control. Peripheral blood was collected at baseline and per cycle (21-28d) respectively. Multiple PCR and NGS on TCR beta chain was used to detect IR. PFS of two groups had a statistical significance (P<0.05), suggesting Nas-T cells prolong patients' PFS. The safety was analyzed from routine blood urine stool test, coagulation function, liver and kidney function. There was no significant difference at baseline (P>0.05). Compared with C group, total protein and albumin in T group had a transient decrease in 3rd, 4th and 5th follow-up respectively (P<0.05), however, It can be recovered autonomously before 6th cycle. Three indexes were examined to illuminate the diversity and clonality of IR. Compared to baseline, T cell repertoir of non-responders and responders after 1st cycle showed significant changes: Shannon 1.14 vs 0.97, P=0.048; Evenness 3.90 vs 0.85, P=0.004; Clonality 1.20 vs 0.70, P=0.017. Elevated Clonality may indicate amplification of tumor specific T cells which could recognize mutant neoantigen specifically. The combined immunotherapy of Nas-T cells and PD1 inhibitors is more effective than PD1 inhibitor alone in prolonging the PFS, and has a good safety. IR Clonality change shows its potential as a predictive biomarker.