Chimeric Costimulatory Antigen Receptor-T Construction Service

Chimeric Antigen Receptor (CAR)-T cell therapy has rapidly gained prominence as a transformative approach in tumor immunotherapy, especially for hematological malignancies. However, extending these successes to solid tumors has proven more challenging due to factors such as the immunosuppressive tumor microenvironment and the heterogeneity of tumor antigens. To address these limitations, Creative Biolabs has pioneered a novel Chimeric Costimulatory Antigen Receptor (CoStAR)-T cell therapy.

Chimeric Costimulatory Antigen Receptor-T Construction Service at Creative Biolabs

Costimulatory signals are pivotal for an effective and sustained anti-tumor response. Their absence can lead to T-cell anergy and dysfunction. Typical CAR-T designs have aimed to enhance these signals, with third-generation CAR-T therapies incorporating dual costimulatory domains showing improved performance over second-generation designs.

The chimeric costimulatory antigen receptor-T Cell therapy development platform developed by Creative Biolabs features a novel synthetic construct with dual CD28 and CD40 signaling domains. This innovative design is tailored to emulate natural co-stimulation, which enhances T-cell activity, including cytokine production, cytotoxicity, and proliferation, without inducing T-cell effector function independently.

Fig.1 Schematic of Chimeric Costimulatory Antigen Receptor-T strategy.

Our One-Stop Services

Creative Biolabs offers a comprehensive suite of services for CoStAR-T cell therapy development, leveraging extensive expertise in both basic and translational immunology. Our services are designed to optimize every step of T-cell engineering:

• Design and Construction

We engineer CoStAR molecules encoding an extracellular domain targeting specific tumor antigens, ensuring costimulatory engagement and amplification of TCR signaling through the optimal CD28 and CD40 intracellular domains.

• Vector Construction and T-cell Transduction

Using advanced lentiviral vectors, we achieve high-efficiency transduction of peripheral T cells from both healthy donors and patient-derived tumor-infiltrating lymphocytes (TILs), ensuring robust expression of CoStARs.

• Functional Validation

CoStAR-T cells are subjected to rigorous functional assays:

Cytokine Secretion: Quantitative analysis of cytokine profiles is performed, demonstrating notable increases in pro-inflammatory cytokines such as IL-2 and TNFα.

Proliferation: Assessment through serial cocultures highlighting enhanced proliferation capabilities.

In Vitro and In Vivo Cytolytic Activity: Verification of targeted cytotoxicity against tumor cells expressing relevant antigens, ensuring specificity and effectiveness.

• Preclinical Evaluation

Our preclinical models are designed to mimic clinical scenarios closely, evaluating the therapeutic efficacy and safety of CoStAR-T cells, including their performance in suppressive tumor microenvironments.

What We Can Offer

Core Advantages

• Grade Vector Production: One-stop fermentation service from lab scale to large-scale industrial fermentation tanks.
• Cell Bank Stability: Assessment and qualification of strain origin and documentation quality. Guaranteed stability of strains in cell banks and large-scale fermentation runs.
• Process Optimization: Fermentation run in batch, fed-batch, or continuous mode. Culture condition optimization to maximize the yield of plasmids or recombinant proteins.

Contact our team today to schedule a consultation and begin engineering the next generation of immunotherapy.

Related Services

Scientific Backing

The scientific foundation of the CoStAR strategy is robust and backed by comprehensive research and empirical data. Research has shown that CoStAR-T cells demonstrated enhanced control of tumor growth and improved survival rates, underscoring their potential for superior therapeutic outcomes in murine models.

Fig.2 In vivo efficacy of CoStAR treatment in a murine xenograft model.¹

Frequently Asked Questions

Creative Biolabs is dedicated to advancing cancer immunotherapy through innovative chimeric costimulatory antigen receptor-T cell therapies. Our comprehensive development services and scientific rigor ensure the transformation of promising research into impactful clinical therapies.

Reference

1. Kalaitsidou, Milena, et al. "Signaling via a CD28/CD40 chimeric costimulatory antigen receptor (CoStAR™), targeting folate receptor alpha, enhances T cell activity and augments tumor reactivity of tumor infiltrating lymphocytes." Frontiers in Immunology 14 (2023): 1256491.