Will In Vivo CAR T Cell Therapy Contribute to a More Effective Therapy for Solid Tumors?

Over the last decade, chimeric antigen receptor (CAR) T cell therapies have demonstrated notable success for the treatment of some aggressive hematological diseases such as lymphoma. However, the same success could not be replicated for solid tumors. This missing efficacy towards solid tumors is frequently linked to the extensive heterogeneity of tumor antigens and rather hostile and complex immunosuppressive tumor microenvironment. Unlike blood cancers where easy circulation facilitates strong interaction with CAR T therapy, such interaction in the case of solid tumors is hampered by poor infiltration, physical barriers in the tumor microenvironment, and limited expansion to solid tumor sites. As well as these intrinsic characteristics of solid tumors, the complex manufacturing process, high production costs, and challenges in quality control and risk management of ex vivo CAR T are behind the increasing role of in vivo CAR T cell therapy. This emerging approach is based on the use of in vivo engineering, using lipid nanoparticles and viral victor platforms. Early results suggest that the use of both platforms is likely to address a number of important limitations associated with ex vivo CAR T. Data furnished by clinical, pharmaceutical, and academic research have put in focus the central role of the tumor microenvironment in solid tumor resistance to most existing therapeutic modalities, including cell therapy. The same research findings underline the need for more innovation to enhance the therapeutic performance of chimeric antigen receptor (CAR) T cell therapies. Such innovation implies more versatile CAR constructs, and more efficient, simpler, and more economic production of engineered T cells, which is likely to be realized through wider application of the in vivo approach.