Emerging prospects of exosomes for cancer treatment

Exosomes are a class of extracellular vesicles of around 100 nm in diameter that are secreted by most cells and contain various bioactive molecules reflecting their cellular origin and mediate intercellular communication. Studies of these exosomal features in tumor pathogenesis have led to the development of therapeutic and diagnostic approaches using exosomes for cancer therapy. Exosomes have many advantages for conveying therapeutic agents such as small interfering RNAs, microRNAs, membrane‐associated proteins, and chemotherapeutic compounds; thus, they are considered a prime candidate as a delivery tool for cancer treatment. Since exosomes also provide an optimal microenvironment for the effective function of immunomodulatory factors, exosomes harboring bioactive molecules have been bioengineered as cancer immunotherapies that can effectively activate each stage of the cancer immunity cycle to successfully elicit cancer‐specific immunity. Researchers from the Korea Institute of Science and Technology (KIST) discuss the advantages of exosomes for treating cancer and the challenges that must be overcome for their successful clinical development.

Cancer immunity cycle

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The multistep process for generating anti‐cancer immunity includes: (1) cancer antigen release from dying cancer cells, (2) cancer antigen presentation by APCs, (3) priming and activation of T cells by APCs in lymph node, (4) T cell trafficking to tumor microenvironment, (5) T cell infiltration into tumors, (6) cancer cell recognition by T cells, and (7) killing of target cancer cells by T cells. Various engineered exosomes can trigger each step of the cancer immunity cycle. Exo‐DOX, exosome containing doxorubicin; Exo‐PTX, paclitaxel‐loaded exosome; Exo‐OV, oncolytic virus‐loaded exosome; TEX, tumor‐derived exosome; DEX, dendritic cell‐derived exosome; mVSVG‐Exo, mVSVG protein expressing exosome; SIRPα‐Exo, SIRPα expressing exosome; Exo‐DNA, DNA‐loaded exosome; Exo‐STING, STING‐loaded exosome; CD40L‐Exo, CD40L expressing exosome; PH20‐Exo, PH20 expressing exosome; CAR‐Exo, CAR‐T cell‐derived exosome; SMART‐Exo, synthetic multivalent antibodies expressing exosome; NK‐Exo, NK cell‐derived exosome; M1‐Exo, M1‐like macrophage‐derived exosome.

Nam G H, Choi Y, Kim G B, Kim S, Kim S A, Kim I S. (2020) Emerging Prospects of Exosomes for Cancer Treatment: From Conventional Therapy to Immunotherapy. Adv Mater 2002440. [article]

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