Dextran-based T-cell expansion nanoparticles for manufacturing CAR T cells with augmented efficacy

Adoptive T cell therapy (ACT) using chimeric antigen receptor (CAR) engineered T cells is currently being explored in multiple cancer types beyond leukemia/lymphoma. A key step in CAR-T cell manufacturing is the activation and expansion of T cells, which facilitates viral transduction, however, may hamper T cell fitness and reducein vivopersistence. We developed “T-Expand” for T cell activation and expansion, comprising dextran-based nanoparticles (NPs) conjugated with anti-CD3 and anti-CD28 antibodies. The NPs triggered robust polyclonal expansion of human T cells with efficiency in the range of commercial microbeads (Dynabeads™). Engineered in presence of T-Expand, CD19 CAR T cells exhibited enhanced proliferative capacity, cytotoxicity and persistence invitro, and furthermore, showed superior anti-lymphoma activity in mouse models resulting in complete tumor clearance at one fourth of the CAR T cell dose. Importantly, T-Expand is biocompatible with no observed toxicity, circumventing removal steps after T cell expansion compared to Dynabeads^TM. As a biocompatible T cell expansion platform, T-Expand simplifies the manufacturing process while enhancing T cell persistence and functionality, thereby holding promise for increasing clinical efficacy of CAR T cell therapy.<fig id="ufig1" position="float" orientation="portrait" fig-type="figure"> <caption>

Graphical abstract/Cover figure:

Illustration of CAR T cell manufacturing using T-Expandsex vivo.

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