CAR Based Immunotherapy of Solid Tumours—A Clinically Based Review of Target Antigens

SIMPLE SUMMARY: Cancer accounts for an increasing number of deaths year on year. However, new immune-based therapies offer promise in the quest to address this unmet need. One approach entails the use of immune white blood cells (usually collected from the patient themselves) and introducing a genetic blueprint that enables these cells to identify and attack cancer cells. These so-called “CAR cells” have proven to be very effective in the treatment of blood cancers. However, solid tumours (which account for 90% of all cancers) are proving more difficult to treat with this approach. One of the key challenges is identifying targets that clearly distinguish between cancer cells and normal, healthy tissue. Here, we have surveyed targets that have been selected for clinical testing of CAR cells in the context of clinical trials. ABSTRACT: Immunotherapy with CAR-engineered immune cells has transformed the management of selected haematological cancers. However, solid tumours have proven much more difficult to control using this emerging therapeutic modality. In this review, we survey the clinical impact of solid tumour CAR-based immunotherapy, focusing on specific targets across a range of disease indications Among the many candidates which have been the subject of non-clinical CAR T-cell research, clinical data are available for studies involving 30 of these targets. Here, we map out this clinical experience, highlighting challenges such as immunogenicity and on-target off-tumour toxicity, an issue that has been both unexpected and devastating in some cases. We also summarise how regional delivery and repeated dosing have been used in an effort to enhance impact and safety. Finally, we consider how emerging armouring systems and multi-targeted CAR approaches might be used to enhance tumour access and better enable discrimination between healthy and transformed cell types.