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 (MNaS-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 MNaS-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 MNaS-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 MNaS-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. Evenness index and Clonality indexe were examined to illuminate the diversity and clonality of IR seperately. Compared to baseline, T cell repertoir of disease-progression patients and no-disease-progression patients after 1st cycle showed significantly different changes: Evenness 3.29 vs 0.85, P = 0.013; Clonality 0.76 vs 1.20, P = 0.015. Elevated Clonality may indicate amplification of tumor specific T cells which could recognize mutant neoantigen specifically.Table: 1163P
Demographic and clinical characteristics of 22 patients
|Characteristic||MNaS-T cells plus PD1 inhibitors plus BSC (N = 11)||PD1 inhibitors plus BSC (N = 11)|
|Disease Progression (N=4)||No Disease Progression (N=7)||Total (N = 11)|
|<60||4 (100)||5 (71.4)||9 (81.8)||6 (54.5)|
|> =60||0||2 (28.6)||2 (18.2)||5 (45.5)|
|Male||3 (75)||3 (42.9)||6 (54.5)||8 (72.7)|
|Female||1 (25)||4 (57.1)||5 (45.5)||3 (27.3)|
|Peripheral IR Diversity--mean (SD)|
|Baseline||0.01 (0.01)||0.07 (0.08)||0.05 (0.07)|
|1st cycle||0.05 (0.05)||0.06 (0.07)||0.05 (0.06)|
|1st cycle / Baseline||3.29 (2.09)||0.85 (0.44)||1.74 (1.71)|
|Baseline||0.32 (0.09)||0.25 (0.18)||0.27 (0.15)|
|1st cycle||0.25 (0.12)||0.27 (0.16)||0.26 (0.14)|
|1st cycle / Baseline||0.76 (0.18)||1.2 (0.27)||1.04 (0.32)|
The combined immunotherapy of MNaS-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.
Clinical trial identification
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All authors have declared no conflicts of interest.