Nat. Med. https://doi.org/10.1038/s41591-018-0040-8 (2018)

In Nature Medicine, Feldman and colleagues use a highly personalized adoptive-therapy approach to successfully treat a patient with metastatic ER+HER2– breast cancer that was refractory to chemotherapy. Whole-exome sequencing of the tumor revealed extensive non-synonymous mutations. After population expansion of tumor-infiltrating lymphocytes (TILs) ex vivo, over 80 billion TILs were re-infused to the patient, in tandem with the cytokine IL-2 and pembrolizumab (antibody to the co-inhibitory molecule PD-1). A total of eleven clonotypes recognized four different tumor neoantigens, most of which persisted long term in the patient (at least 17 months). Resolution of all tumor lesions was seen at 1 year after TIL infusion, and the patient remained clear >22 months later. This demonstrates the beneficial results that can be achieved with a highly personalized TIL adoptive-transfer approach.