Current and future directions for tumor infiltrating lymphocyte therapy for the treatment of solid tumors

Cancer is the second leading cause of death in the USA. Over 90% of cancers involve solid tumors while 10% are hematological malignancies. Adoptive cell transfer (ACT) utilizing chimeric antigen receptor (CAR) T cells has recently been approved as treatment for a subset of hematologic cancers, changing the prospects of a small fraction of cancer patients. Patients with solid tumors though have not received significant benefit from CAR T therapy and many remain without therapeutic options after progressing on standard of care, including immune checkpoint inhibitors. First tested more than 30 years ago and optimized over the decades, ACT with tumor-infiltrating lymphocytes (TIL) was shown to be remarkably efficient for the treatment of metastatic melanoma, and is now re-emerging as a promising therapeutic option for heavily pre-treated patients with melanoma and other solid tumors. TIL therapy is a one-time treatment that involves the adoptive transfer of autologous T cells isolated from the tumor tissue and expanded ex vivo to a patient who has been lymphodepleted to remove their immunosuppressive tumor microenvironment which is supportive of a tumor in a cancer patient. The authors have established a streamlined GMP process for the production of TIL and demonstrated efficacy of the product in several highly unmet medical need patient populations, as evidenced by durable responses as assessed by RECIST 1.1. Two pivotal clinical studies in melanoma and cervical cancer indications are ongoing to support bringing this product to the market.

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