Exosomes (versatile, cell-derived nanovesicles naturally endowed with exquisite target-homing specificity and the ability to surmount in vivo biological barriers) hold substantial promise for developing exciting approaches in drug delivery and cancer immunotherapy. Specifically, bioengineered exosomes are being successfully deployed to deliver potent tumoricidal drugs (siRNAs and chemotherapeutic compounds) preferentially to cancer cells, while a new generation of exosome-based therapeutic cancer vaccines has produced enticing results in early-phase clinical trials. Here, reseachers from the National University of Singapore review the state-of-the-art technologies and protocols, and discuss the prospects and challenges for the clinical development of this emerging class of therapeutics.
Scope of Exosomal Therapeutics for Future Cancer Treatment
Two broad exosome-based therapeutic modalities can be surmised from current research directions: (A) Trojan horse-like exosomal formulations designed to insidiously deliver a potent antitumor payload, including chemotherapeutic drugs and novel nucleic acid therapies, to malignant cells; and (B) cancer vaccines to promote the expansion and activation of tumor-specific cytotoxic T lymphocytes (CTLs), and reinstatement of CTL- and polarized TH1-mediated anticancer immunosurveillance. Abbreviations: CD80/86, cluster of differentiation 80 and 86 protein; IL-15Rα, interleukin 15 receptor, alpha subunit; MHC-I and -II, major histocompatibility complex class I and II; NK cells, natural killer cells; NKG2D, natural killer cell lectin-like receptor K1; RES, reticuloendothelial system (also known as mononuclear phagocyte system; MPS); ULBP1, UL16-binding protein 1 (also known as NKG2D-ligand 1).
Exosomes are extracellular cell-derived phospholipid nanovesicles that function as signalosomes, transmitting prodigious amounts of bioactive molecules to specific recipient tissues. Their intriguing endogenous functionalities have galvanized momentous efforts to exploit them as novel anticancer therapeutics.
Exosomes may offer a tractable, bioinspired system for targeted drug delivery, which could improve the therapeutic indices of conventional cytotoxic chemotherapeutic agents, and help to realize the enormous potential of gene therapy in oncology.
Owing to their immunomodulatory potential, exosomes may also be deployed in innovative immunological approaches to activate adaptive and innate effector cell-mediated anticancer immunosurveillance.