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

TL;DR

A new dextran-based nanoparticle platform improves T cell expansion for CAR T cell therapy, enhancing potency and reducing required doses.

Contribution

A biocompatible nanoparticle system for T cell activation and expansion that simplifies manufacturing and improves CAR T cell efficacy.

Findings

T-Expand nanoparticles enable efficient T cell expansion comparable to commercial microbeads.

CAR T cells produced with T-Expand show enhanced proliferation, cytotoxicity, and persistence.

T-Expand-based CAR T cells achieve complete tumor clearance at one-fourth the dose in mouse models.

Abstract

Adoptive T cell therapy 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 reduce in vivo persistence. “T-Expand” is developed for T cell activation and expansion, comprising dextran-based nanoparticles conjugated with anti-CD3 and anti-CD28 antibodies. The nanoparticles trigger robust polyclonal expansion of human T cells with efficiency in the range of commercial microbeads (Dynabeads™). Engineered in the presence of T-Expand, CD19 CAR T cells display enhanced proliferative capacity, cytotoxicity and persistence in vitro, and furthermore, exhibit potent 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 DynabeadsTM. As a biocompatible T cell expansion platform, T-Expand simplifies the manufacturing process while enhancing T cell persistence and functionality, and thereby holds promise for increasing clinical efficacy of CAR T cell therapy.

T-cell therapies have huge potential but face technical limitations. Here, the authors report on a dextran-based nanoparticle platform that efficiently expands T cells, enhances CAR T-cell potency, persistence, and anti-tumour efficacy, using simpler and faster methods than current techniques.

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