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

Area of Science:

• Immunology
• Biotechnology
• Oncology

Background:

• Adoptive T cell therapy, particularly chimeric antigen receptor (CAR) T cell therapy, shows promise for various cancers.
• Current CAR T cell manufacturing involves T cell activation and expansion, which can negatively impact T cell fitness and persistence.
• Existing expansion methods, like microbeads, may require additional removal steps and can affect T cell quality.

Purpose of the Study:

• To develop and evaluate a novel T cell expansion platform, T-Expand, for CAR T cell therapy.
• To assess the impact of T-Expand on T cell activation, expansion, fitness, and in vivo efficacy.
• To compare T-Expand with commercial microbead-based expansion methods.

Main Methods:

• Development of dextran-based nanoparticles conjugated with anti-CD3 and anti-CD28 antibodies (T-Expand).
• Assessment of T cell expansion efficiency and T cell phenotype after T-Expand treatment.
• In vitro evaluation of engineered CD19 CAR T cell proliferative capacity, cytotoxicity, and persistence.
• In vivo testing of CAR T cell therapy efficacy in mouse lymphoma models.

Main Results:

• T-Expand nanoparticles induced robust polyclonal T cell expansion comparable to commercial microbeads.
• CAR T cells engineered with T-Expand exhibited enhanced proliferation, cytotoxicity, and persistence in vitro.
• In vivo studies showed potent anti-lymphoma activity, achieving complete tumor clearance at a reduced CAR T cell dose.
• T-Expand demonstrated biocompatibility with no observed toxicity and eliminated the need for post-expansion removal steps.

Conclusions:

• T-Expand serves as an effective and biocompatible platform for T cell activation and expansion in CAR T cell manufacturing.
• This approach simplifies the production process while improving CAR T cell persistence and functionality.
• T-Expand holds significant potential for enhancing the clinical efficacy of CAR T cell therapy in cancer treatment.