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CAR Therapies: Ex Vivo and In Vivo Potential of Exosomes and Biomimetic Nanoparticles
by
, , , , and
Ekaterina Tkachenko
1, 
Natalia Ponomareva
1,
Konstantin Evmenov
1,2,
Artyom Kachanov
1,
Sergey Brezgin
1,2,
Anastasiya Kostyusheva
1,
Vladimir Chulanov
2,3,4
,
Elena Volchkova
4,
Alexander Lukashev
5,6,
Dmitry Kostyushev
1,2,7,*
and
Peter Timashev
8 1
Laboratory of Genetic Technologies, Martsinovsky Institute of Medical Parasitology, Tropical and Vector-Borne Diseases, Sechenov University, Moscow 119435, Russia
2
Engelhardt Institute of Molecular Biology, Russian Academy of Science, Moscow 119991, Russia
3
Laboratory of Experimental Therapy of Infectious Diseases, Martsinovsky Institute of Medical Parasitology, Tropical and Vector-Borne Diseases, Sechenov University, Moscow 119435, Russia
4
Department of Infectious Diseases, Sechenov University, Moscow 119435, Russia
5
Martsinovsky Institute of Medical Parasitology, Tropical and Vector Borne Diseases, Sechenov University, Moscow 19991, Russia
6
Research Institute for Systems Biology and Medicine, Moscow 117246, Russia
7
Faculty of bioengineering and bioinformatics, Lomonosov Moscow State University, Moscow 119192, Russia
8
Institute for Regenerative Medicine, I. M. Sechenov First Moscow State Medical University, Moscow 119991, Russia
*
Author to whom correspondence should be addressed.
Cancers 2025, 17(23), 3766; https://doi.org/10.3390/cancers17233766
Submission received: 5 October 2025
/
Revised: 17 November 2025
/
Accepted: 20 November 2025
/
Published: 25 November 2025
(This article belongs to the Section Cancer Immunology and Immunotherapy)
Simple Summary
The introduction of chimeric antigen receptors (CAR) into T-cells has proven highly effective against hematologic malignancies, frequently leading to complete remissions. In contrast, the success of CAR-T therapy in solid tumors has been modest. This review focuses on the emerging promise of biomimetic nanoparticles to overcome this hurdle by enabling highly efficient CAR-T cell programming, both ex vivo and in vivo. We synthesize the current landscape, reviewing the technological challenges, limitations, and ongoing clinical progress of this innovative strategy.
Abstract
Chimeric antigen receptor (CAR) therapy represents a promising modality for treating cancer and autoimmune diseases, employing genetically engineered immune cells. Despite remarkable clinical outcomes, its broad implementation is constrained by significant challenges, including toxicity, limited specificity, and complexities associated with genetic material delivery. Biological nanoparticles, such as exosomes, virus-like particles, and biomimetic nanostructures, possess unique properties that can address these limitations. These nanoplatforms enable targeted delivery of genetic constructs, mitigate the risk of cytokine release syndrome, modulate CAR cell activity, and can function as biosensors. Furthermore, they facilitate non-viral, in vivo CAR cell engineering, streamlining the process compared to conventional ex vivo methods. The advancement of in vivo strategies underscores the critical need to overcome toxicity hurdles inherent to current CAR-T platforms. In this context, exosomes and biomimetic nanoparticles offer considerable potential due to their innate biocompatibility, programmability, and versatile cargo capacity for payloads like mRNA and circular RNA. This review comprehensively outlines contemporary genetic platforms for CAR expression and examines the opportunities presented by biological delivery vehicles. It focuses on recent achievements and revisits fundamental CAR principles through the lens of emerging technologies aimed at confronting persistent challenges in the field.
