Defining precision cellular immunotherapy—seeking biomarkers to predict and optimize outcomes of T cell therapies in cancer

Shuting Han, Who-Whong Wang, Esdy Rozali, Han Chong Toh


Cellular immunotherapy, harnessing the patient’s own and donor immune cells, has emerged as a form of highly personalized treatment in cancer. Adoptive transfer of genetically engineered T cells modified to express chimeric antigen receptor (CAR) has demonstrated remarkable anti-tumor response and long-term remissions in selected hematologic malignancies. However, cancer relapse is still a challenge in some of these patients, and CAR T cell therapy is still investigational and of limited efficacy against solid tumors. On the other hand, tumor infiltrating lymphocyte (TIL) therapy, genetically modified T cell receptor (GM-TCR) therapy and viral-specific T cell therapy are emerging treatment options in solid organ cancers. There is a great interest and increasing effort towards studying biomarkers that can predict for improved outcomes of patients undergoing cellular therapy, still a nascent, emerging field. Identification of such biomarkers may allow enrichment strategies to improve clinical trial design aimed at accelerating clinical development and approvals of such therapies. Given the current high financial costs of cellular therapy, biomarkers can potentially better identify patients that derive maximum benefit as well as potentially reducing pressure on reimbursement-based healthcare systems. Here, we review the current understanding and body of literature on biomarkers for cellular therapy, with a specific focus on T cell therapies. Biomarkers predictive for cellular therapy-based adverse events have been reviewed elsewhere and is not discussed herein.