Immunotherapy to treat cancer








Immunotherapy to treat cancer starts decades ago. The breakthrough example is that allogeneic hematopoietic stem cell transplantation to cure relapsed/refractory hematologic malignancies. Allogeneic hematopoietic stem cell transplantation demonstrates the concept of graft versus leukemia effect and further confirmed by donor lymphocyte infusion. In addition, T cells can be genetically modified to target tumors through the expression of a chimeric antigen receptor (CAR). The basic design of CAR T cells consists of two fundamental domains: the antigen-binding portion (commonly composed of a single-chain variable fragment [scFv] derived from a monoclonal antibody [mAb]) joined to one or more intracellular T-cell signaling domains. The clinical benefit of CAR T cells has now been reported by several groups targeting the CD19 antigen in patients with refractory hematologic malignancies even failed allogeneic hematopoietic stem cell transplantation. In solid tumors, long term survival of some advanced or disseminated melanoma or renal cell carcinoma is encountered with interferon or interleukin. Cancer cells escape immune surveillance by blunt T cell response. The response of T cell is under regulation by “immune checkpoints”, CTLA-4 and PD-1 play important roles in the T cell activation. Cancer cells could interfere these pathways to escape T cell. Just 5 years ago, the immunotherapy drug ipilimumab( monoclonal antibody to CTLA-4 ) was hailed as the first treatment to improve the survival of people with advanced melanoma. Today, newer immunotherapies directed against programmed death-1 (PD-1) and programmed death-ligand 1 (PD-L1) proteins seem to be as or even more effective, while causing fewer adverse effects. Additional studies have suggested that combining immunotherapy agents from these two different classes of drugs may provide even more benefit, although the combined regimens can be more toxic. Research reported in 2015 showed that immunotherapies can improve outcomes for difficult-to-treat cancers.