Recognition of Non-synonymous Somatic Mutations by Tumor Infiltrating Lymphocytes (TIL) in Metastatic Breast Cancer

摘要

Adoptive transfer of tumor infiltrating lymphocytes (TIL) can mediate long-term durable regression in patients with metastatic melanoma, a type of cancer which is characterized by a high number of mutated genes and pronounced lymphocytic infiltrate. Common epithelial cancers, including breast cancer, express far fewer somatic mutations than melanoma and the level of reactive TIL is limited. This pilot study investigated the ability to identify personalized non-synonymous somatic mutations in metastatic breast cancer lesions, to grow TIL that recognize the products of these mutations, and to adoptively transfer these TIL into patients with metastatic breast cancer, refractory to other treatments. Metastatic and primary tumor lesions from thirty one patients with breast cancer were studied in the Surgery branch, NCI, N1H and all of them were found to contain and express mutated genes (range: 4-1788 , median: 99). TIL recognized at least one (range: 1-10, median: 3) mutated product in 21 of 32 the patients (66%). Five evaluable patients with metastatic breast cancer, refractory to prior multiple lines of treatment, were treated with enriched mutation-reactive TIL in our ongoing pilot clinical trial. The immunogenicity of mutations in the majority of the patients with metastatic breast cancer can be the platform for an adoptive T cell transfer therapeutic approach targeting those mutated genes.