Personalized immunotherapy for non-small cell lung cancer through identification of tumor-specific mutations by next generation sequencing and adoptive transfer of tumor infiltrating lymphocytes that recognize neoantigens

Abstract

Patients with metastatic melanoma can be successfully treated with adoptive transfer of tumor infiltrating lymphocytes (TIL). In 93 patients with over 5 year follow-up, the overall response rate was 56% and 20% achieved durable complete responses persisting in excess of 7 years. However, past attempts to apply TIL therapy to other solid cancers have not been successful and low frequency of tumor-specific T cells in other cancers has been suspected as a reason. Recent progress in Next Generation Sequencing technol- ogy has enabled us to analyze genetic mutations in an indi- vidual patient’s tumor and identify immune cells that are reactive to these mutation-encoded neoantigens. The potential of this therapeutic approach recently was illu- strated in a patient with cholangiocarcinoma who experi- enced major tumor regression when given such T cells. NSCLC is a cancer with a high number of genetic muta- tions and a recent report suggests that clinical response of NSCLC to anti-PD1 antibody therapy is positively asso- ciated with the number of genetic mutations