Advancements and challenges in developing in vivo CAR T cell therapies for cancer treatment

Thuy Anh Bui; Haoqi Mei; Rui Sang; David Gallego Ortega; Wei Deng

doi:10.1016/j.ebiom.2024.105266

Advancements and challenges in developing in vivo CAR T cell therapies for cancer treatment

EBioMedicine. 2024 Aug:106:105266. doi: 10.1016/j.ebiom.2024.105266. Epub 2024 Aug 1.

Authors

Thuy Anh Bui¹, Haoqi Mei², Rui Sang³, David Gallego Ortega⁴, Wei Deng⁵

Affiliations

¹ School of Biomedical Engineering, University of Technology Sydney, Ultimo, NSW 2007, Australia; Whitlam Orthopaedic Research Centre, Ingham Institute for Applied Medical Research, Liverpool, NSW 2170, Australia; School of Clinical Medicine, Faculty of Medicine, University of New South Wales Sydney, Kensington, NSW 2052, Australia.
² School of Biomedical Engineering, University of Technology Sydney, Ultimo, NSW 2007, Australia.
³ Graduate School of Biomedical Engineering, ARC Centre of Excellence in Nanoscale Biophotonics, Faculty of Engineering, UNSW Sydney, NSW 2052, Australia.
⁴ School of Biomedical Engineering, University of Technology Sydney, Ultimo, NSW 2007, Australia; Garvan Institute of Medical Research, The Kinghorn Cancer Centre, Darlinghurst, NSW 2010, Australia; School of Clinical Medicine, Faculty of Medicine, University of New South Wales Sydney, Kensington, NSW 2052, Australia.
⁵ School of Biomedical Engineering, University of Technology Sydney, Ultimo, NSW 2007, Australia; Graduate School of Biomedical Engineering, ARC Centre of Excellence in Nanoscale Biophotonics, Faculty of Engineering, UNSW Sydney, NSW 2052, Australia. Electronic address: wei.deng@uts.edu.au.

Abstract

The Chimeric Antigen Receptor (CAR) T cell therapy has emerged as a ground-breaking immunotherapeutic approach in cancer treatment. To overcome the complexity and high manufacturing cost associated with current ex vivo CAR T cell therapy products, alternative strategies to produce CAR T cells directly in the body have been developed in recent years. These strategies involve the direct infusion of CAR genes via engineered nanocarriers or viral vectors to generate CAR T cells in situ. This review offers a comprehensive overview of recent advancements in the development of T cell-targeted CAR generation in situ. Additionally, it identifies the challenges associated with in vivo CAR T method and potential strategies to overcome these issues.

Keywords: Cancer; Gene delivery; Gene editing; In vivo CAR-T.

Publication types

Review

MeSH terms

Animals
Genetic Vectors / administration & dosage
Genetic Vectors / genetics
Humans
Immunotherapy, Adoptive* / methods
Neoplasms* / genetics
Neoplasms* / immunology
Neoplasms* / therapy
Receptors, Antigen, T-Cell / genetics
Receptors, Antigen, T-Cell / immunology
Receptors, Chimeric Antigen* / genetics
Receptors, Chimeric Antigen* / immunology
T-Lymphocytes* / immunology
T-Lymphocytes* / metabolism

Substances

Receptors, Chimeric Antigen
Receptors, Antigen, T-Cell