Abstract 3015
Background
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.
Methods
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.
Results
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) | |||
| Age--no.(%) | |||||
| <60 | 4 (100) | 5 (71.4) | 9 (81.8) | 6 (54.5) | |
| > =60 | 0 | 2 (28.6) | 2 (18.2) | 5 (45.5) | |
| Sex--no.(%) | |||||
| Male | 3 (75) | 3 (42.9) | 6 (54.5) | 8 (72.7) | |
| Female | 1 (25) | 4 (57.1) | 5 (45.5) | 3 (27.3) | |
| Previous treatments--no. | |||||
| Chemotherapy | 4 | 7 | 11 | 11 | |
| Targeted therapy | 4 | 7 | 11 | 11 | |
| ECOG--no.(%) | |||||
| 0 | 0 | 0 | 0 | 0 | |
| 1 | 1 | 6 | 7 | 6 | |
| ≥2 | 3 | 1 | 4 | 5 | |
| Stage--no. | IV | 4 | 7 | 11 | 11 |
| Peripheral IR Diversity--mean (SD) | |||||
| Evenness | |||||
| 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) | ||
| Clonality | |||||
| 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) |
Conclusions
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
Legal entity responsible for the study
J. Shunchang.
Funding
Has not received any funding.
Editorial Acknowledgement
Disclosure
All authors have declared no conflicts of interest.
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