Optimising CAR T therapy for the treatment of solid tumors

Adoptive immunotherapy using chimeric antigen receptor (CAR)-engineered T cells has proven transformative in the management of B cell and plasma cel derived malignancies. However, solid tumors have largely proven to be resistant to this therapeutic modality. Challenges include the paucity of safe target antigens, heterogeneity of target expression within the tumor, difficulty in delivery of CAR T cells to the site of disease, poor penetration within solid tumor deposits and inability to circumvent the array of immunosuppressive and biophysical barriers imposed by the solid tumor microenvironment.

Literature was reviewed on the PubMed database, excluding occasional papers which were not available as open access publications or through other means.

Here, we have surveyed the large body of technological advances that have been made in the quest to bridge the gap toward successful deployment of CAR T cells for the treatment of solid tumors. These encompass the development of more sophisticated targeting strategies to engage solid tumor cells safely and comprehensively, improved drug delivery solutions, design of novel CAR architectures that achieve improved functional persistence and which resist physical, chemical and biological hurdles present in tumor deposits. Prospects for combination therapies that incorporate CAR T cells are also considered.