Adoptive T-Cell Therapy for Cancer

Abstract

Recent developments have demonstrated that immunotherapies are capable of achieving durable antitumor responses in patients with metastatic cancer. One modality that has been able to induce durable complete regressions in patients with melanoma has been adoptive cell therapy (ACT). This has slowly been expanded to other cancer types using new approaches such as genetically engineered T-cells and other methods of antigen targeting. It now appears that immune targeting of mutated "neoantigens" plays a major role in successful ACT, as well as in other immunotherapies such as checkpoint inhibitors. This realization presents not only new challenges to ACT but also new opportunities in that all tumors now may have potential antigens to attack that can be revealed by tumor genomic sequencing. There are a variety of exciting approaches to translate these new findings into clinical trials applying ACT to the majority of cancer types.

Keywords: Adoptive cell therapy; Immunotherapy; Neoantigens; T-cell transfer; Tumor antigens; Tumor infiltrating lymphocytes.

Figure 1

Patient with an NY-ESO-1-expressing metastatic synovial cell sarcoma showing ongoing regression of lung metastases and a large pelvic primary tumor after a single adoptive transfer of autologous T-cells genetically engineered with a T-cell receptor recognizing NY-ESO-1. (A) Pretreatment scans, (B) 5 months posttreatment, and(C) 5 years posttreatment.

Figure 2

Patient with metastatic cholangiocarcinoma after adoptive T-cell transfer of tumor infiltrating lymphocytes highly selected (95% clonal) for a CD4+ clone reactive with a mutated epitope in ERBB2 interactive protein, expressed by her cancer. Pre-treatment scans of lung and liver (left) and matching scans 20 months later (right) are shown.