Neoantigens are derived from tumor specific mutations and presented by MHC on cancer cells. The set of neoantigens likely bypass immune tolerance and less likely induce autoimmunity because they are absent from normal cells. Targeting multiple neoantigens may significantly enhance the clinical efficacy of anti-tumor treatment with less toxicity. We present the proof-of-concept clinical application of personalized neoantigens induced T cell therapy.
This open-label phase Ia clinical trial is designed to test the safety and objective response of the tumor specific antigen-induced cytotoxic T lymphocytes (TSA-CTL). This study will enroll 9 advanced melanoma patients. Participants should have measurable metastases with at least one lesion that is resectable or tumor biopsies for DNA and RNA extraction. For each patient, we generate autologous TSA-CTLs based on neoantigens which identified through machine learning approaches with exome sequencing. Patients will receive 6 doses of TSA-CTL infusion. Toxicity (endpoint 1) will be defined by Common Terminology Criteria for Adverse Events v5.0, and objective response (endpoint 2) will be determined by the Response Evaluation Criteria in Solid Tumors.
Seven patients have been enrolled so far and three of them have completed 3 cycles of TSA-CTL infusion. The fifth patient display pruritus grade 1. No other related adverse events just after the treatment were observed. We detected neoantigen-specific CD8+ T cells in peripheral blood through pMHC tetramer and found that neoantigen-specific CD8+ T cell increased after the TSA-CTL infusions for the third patient and the fifth patient. After three cycles of TSA-CTL infusion, the third and the fourth patient was assessed as SD with three metastasis’ regression and PR, respectively. Further treatment and analyses are ongoing.
No major direct side effects are observed. Although with very limited trial subjects, a few patients did show favorable responses. Our study highlights the promise of personalized cell therapy for tumor-specific T cells and provide guidance for the future development. Clinical trial information: NCT02959905.
Clinical trial identification
NCT02959905; Release date: November 9, 2016.
Legal entity responsible for the study
B. Li, S. Qiu: Employee: BGI Tech Solutions (Hong Kong Co. Ltd)