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Hung Trinh: Direct in vivo CAR T cell engineering

Hung Trinh/LinkedIn

Jan 28, 2025, 20:25

Hung Trinh: Direct in vivo CAR T cell engineering

Hung Trinh, CMC/MFG Consultant and Managing Director at Vertex Biopharm Consulting, posted on LinkedIn about recent paper by Lauralie Short et al., titled “Direct in vivo CAR T cell engineering” published on Trends in Pharmacological Sciences.

Authors: Lauralie Short, Robert A. Holt, Pieter R. Cullis, Laura Evgin

“Direct in vivo CAR T cell engineering

Adoptive cell therapy using chimeric antigen receptor (CAR) T cells is effective against B cell malignancies, however, the complex manufacturing process and financial realities constrain the scalability of the approach.
The in vivo generation of CAR T cells, and possibly other immune cells, using off-the-shelf products therefore has numerous logistical and functional advantages. In preclinical models, in vivo gene delivery using nanoparticles or viral vectors has yielded CAR T cells with therapeutic equivalency to ex vivo generated CAR T cells. Ongoing research efforts are attempting to determine how to best target and leverage effector cells of interest (T cells, macrophages etc.), understand how direct in vivo CAR generation interfaces with other immune cells, and optimize design elements of the viral vectors or nanoparticle and nucleic acid formulations.

T cells modified to express intelligently designed chimeric antigen receptors (CARs) are exceptionally powerful therapeutic agents for relapsed and refractory blood cancers and have the potential to revolutionize therapy for many other diseases. To circumvent the complexity and cost associated with broad-scale implementation of ex vivo manufactured adoptive cell therapy products, alternative strategies to generate CAR T cells in vivo by direct infusion of nanoparticle-formulated nucleic acids or engineered viral vectors under development have received a great deal of attention in the past few years. Here, we outline the ex vivo manufacturing process as a motivating framework for direct in vivo strategies and discuss emerging data from preclinical models to highlight the potency of the in vivo approach, the applicability for new disease indications, and the remaining challenges associated with clinical readiness, including delivery specificity, long term efficacy, and safety.”