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Review
. 2024 Sep 26;3(9):e70011.
doi: 10.1002/jex2.70011. eCollection 2024 Sep.

Exploring the potential of the convergence between extracellular vesicles and CAR technology as a novel immunotherapy approach

Ofir Bar  1 , Angel Porgador  1 , Tomer Cooks  1
Affiliations
Review

Exploring the potential of the convergence between extracellular vesicles and CAR technology as a novel immunotherapy approach

Ofir Bar et al. J Extracell Biol. .

Abstract

Cancer therapy is a dynamically evolving field, witnessing the emergence of innovative approaches that offer a promising outlook for patients grappling with persistent disease. Within the realm of therapeutic exploration, chimeric antigen receptor (CAR) T cells as well as CAR NK cells, have surfaced as novel approaches, each possessing unique attributes and transformative potential. Immune cells engineered to express CARs recognizing tumour-specific antigens, have shown remarkable promise in treating terminal cancers by combining the precision of antibody specificity with the potent cytotoxic function of T cells. However, their application in solid tumours is still in its nascent stages, presenting unique major challenges. On the same note, CAR NK cells offer a distinct immunotherapeutic approach, utilizing CARs on NK cells, providing advantages in safety, manufacturing simplicity, and a broader scope for cancer treatment. Extracellular vesicles (EVs) have emerged as promising therapeutic agents due to their ability to carry crucial biomarkers and biologically active molecules, serving as vital messengers in the intercellular communication network. In the context of cancer, the therapeutic potential of EVs lies in delivering tumour-suppressing proteins, nucleic acid components, or targeting drugs with precision, thereby redefining the paradigm of precision medicine. The fusion of CAR technology with the capabilities of EVs has given rise to a new therapeutic frontier. CAR T EVs and CAR NK EVs, leveraging the power of EVs, have the potential to alleviate challenges associated with live-cell therapies. EVs are suggested to reduce the side effects linked to CAR T cell therapy and hold the potential to revolutionize the penetrance in solid tumours. EVs act as carriers of pro-apoptotic molecules and RNA components, enhancing immune responses and thereby expanding their therapeutic potential. In this review article, we navigate dynamic landscapes, with our objective being to evaluate comparative efficacy, safety profiles, manufacturing complexities, and clinical applicability.

Keywords: NK cells; T cells; chimeric antigen receptors; extracellular vesicles; immunotherapy.

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Conflict of interest statement

The authors declare no conflicts of interest.

Figures

FIGURE 1
FIGURE 1
CAR on the surface or EVs released by T or NK cells. EVs are formed through a series of regulated steps within the endocytic pathway. The process starts with plasma membrane internalization through endocytosis, followed by maturation of early endosomes into multivesicular bodies (MVBs) with intraluminal vesicles (ILVs). ILVs within MVBs can either be degraded within lysosomes or released as exosomes regulated by various molecules and proteins, including Rab GTPases, ESCRT proteins, and lipids. When T cells or NK cells undergo CAR generation, the chimeric receptor localized to the plasma membrane can be invaginated and sorted into the MVBs, eventually part of the exosomal release. Alternatively, the CAR can be produced and release from the Golgi in vesicles that in turn will contain the CAR and fuse with the in any step of the endosomal process.
FIGURE 2
FIGURE 2
Comparing advantages and disadvantages of CAR and CAR EVs in the context of therapy.
See this image and copyright information in PMC

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