T cell engineering as therapy for cancer and HIV: our synthetic future

Abstract

It is now well established that the immune system can control and eliminate cancer cells. Adoptive T cell transfer has the potential to overcome the significant limitations associated with vaccine-based strategies in patients who are often immune compromised. Application of the emerging discipline of synthetic biology to cancer, which combines elements of genetic engineering and molecular biology to create new biological structures with enhanced functionalities, is the subject of this overview. Various chimeric antigen receptor designs, manufacturing processes and study populations, among other variables, have been tested and reported in recent clinical trials. Many questions remain in the field of engineered T cells, but the encouraging response rates pave a wide road for future investigation into fields as diverse as cancer and chronic infections.

Keywords: cancer; immunotherapy; synthetic biology.

Figure 1.

T cells can be engineered to have retargeted specificity for tumours. Bispecific T cells are created by introduction of genes that encode T-cell receptors (TCRs) and chimeric antigen receptors (CARs) of desired specificity and affinities for tumours. CARs target surface antigens in an MHC-independent fashion. The T cells retain expression of the endogenous TCR, unless this is knocked down by various approaches. Costim, cosignalling domain such as CD28, ICOS or 4-1BB; LAT, linker for activation of T cells; scFv, single-chain variable fragment; ZAP70, ζ chain associated protein kinase 70 kDa. (Online version in colour.)