# Harnessing CAR-Extracellular Vesicles for Next-Generation Cancer Immunotherapy

## TL;DR

This review explores how extracellular vesicles from CAR-engineered immune cells can be used to improve cancer immunotherapy by delivering anticancer agents and modulating immune responses.

## Contribution

The paper highlights the novel use of CAR-derived extracellular vesicles as a cell-free platform for targeted cancer therapy.

## Key findings

- CAR-derived extracellular vesicles can deliver anticancer mediators to tumor environments.
- These vesicles show potential for modulating immune responses and reducing systemic toxicity.
- They can serve as targeted delivery vehicles for chemotherapeutic agents.

## Abstract

Cancer immunotherapy has experienced substantial progress in recent years, particularly with the advancement of chimeric antigen receptor (CAR) technology, which enables immune cells to selectively target tumor-associated antigens. CARs, now in their fifth generation, are engineered by combining monoclonal antibody fragments with signaling and co-stimulatory domains and have been successfully applied to T cell, natural killer (NK) cell, and macrophage-based therapies. Notable clinical successes, such as tisagenlecleucel and lisocabtagene maraleucel underscore the therapeutic potential of CAR-T, CAR-NK and CAR-macrophages (CAR-Ms), which are currently being evaluated in numerous clinical trials. One promising extension of this approach involves the use of extracellular vesicles (EVs) derived from these immune cells. These nano-sized vesicles offer a cell-free platform to deliver diverse anticancer mediators, addressing the complex and dynamic nature of tumor environments. In this review, we examine the therapeutic potential and immunogenic properties of CAR-derived EVs, along with their role in modulating immune responses. Furthermore, we explore their application as targeted delivery vehicles for chemotherapeutic agents, with the goal of enhancing anti-tumor efficacy while minimizing systemic toxicity.