Exosomes in review: A new frontier in CAR-T cell therapies

Abstract

Exosomes are extracellular vehicles that facilitate intra-cellular communication via transport of critical proteins and genetic material. Every exosome is intrinsically reflective of the cell from which it was derived and can even mimic effector functions of their parent cells. In recent years, with the success of CAR-T therapies, there has been growing interest in characterizing exosomes derived from CAR-T cells. CAR exosomes contain the same cytotoxic granules as their parent cells and have demonstrated significant anti-tumor activity in vitro and in animal models. Moreover, infusion of CAR exosomes in animal models did not generate cytokine release syndrome. Conversely, there are also novel bispecific antibodies which target tumor-derived exosomes in hopes of derailing immunosuppressive pathways mediated by exosomes produced from malignant cells. The two most promising examples include (a) BsE CD73 x EpCAM which binds and inhibits exosomal CD73 to suppress production of immunosuppressant adenosine and (b) BsE CD3 x PD-L1 which targets exosomal PD-L1 within the tumor microenvironment to guide cytotoxic T-cells towards tumor cells. As our understanding of exosome biology continues to evolve, opportunities for advances in cellular therapies will grow in tandem.