alfaCAR-T^TM: CAR-T Cells with Sustained Therapeutic Response

CAR‑T cell therapy has revolutionized the treatment of hematological and solid tumors, sparking global interest in cancer R&D. Alfa Cytology, a global leader in bioreagents and a preclinical research service provider, offers comprehensive solutions from early target discovery to preclinical development. Our proprietary alfaCAR‑T™ platform is engineered for enhanced durability and persistent efficacy, delivering robust, long‑lasting anti‑tumor responses.

What are Chimeric Antigen Receptors (CARs)?

Chimeric antigen receptors (CARs) are engineered constructs designed to augment natural T cell receptors (TCRs). They comprise four principal components:

An extracellular antigen-binding domain: The extracellular domain, a single-chain variable fragment (scFv), is able to specifically recognize tumor surface antigens.
A hinge or spacer region: The hinge or spacer region determines the flexibility of the extracellular portion of CARs, which in turn influences the accessibility of epitopes that can be targeted by the receptor.
A transmembrane domain: The transmembrane domain not only anchors the CAR to the cell membrane but also affects its stability and expression levels.
One or more intracellular signaling domains: Typically containing a CD3ζ chain, this region of the CAR plays a vital role in triggering and sustaining the signaling cascade that initiates a plethora of different mechanisms leading to the apoptosis of cancer cells

Fig.1 The introduction of CAR-T cells. (Yang, Y. H., et al., 2022)

Classification and Evolution of CAR-T Cells

Currently, five generations of CAR‐T have been developed with different characteristics.

Type	Brief Description
First Generation CAR-T	Contain only the CD3ζ signaling domain, resulting in limited T cell activation, expansion, and persistence.
Second Generation CAR-T	Incorporate a costimulatory domain (e.g., CD28, 4-1BB, or ICOS) alongside CD3ζ to enhance T cell activation, proliferation, and persistence.
Third Generation CAR-T	Combine multiple costimulatory domains (e.g., CD28/ICOS and 4-1BB/CD27/OX-40) with CD3ζ, though they do not consistently demonstrate superior activation compared to the second generation.
Fourth Generation CAR-T	Add an NFAT-driven inducible cytokine module (e.g., IL-12) to the second-generation design, enhancing anti-tumor efficacy and modifying the tumor microenvironment.
Fifth Generation CAR-T	Integrate an IL-2Rβ domain and transcription factors (STAT3/STAT5) between the costimulatory and CD3ζ domains to further boost T cell proliferation, persistence, and anti-tumor activity.

Introduction to Our alfaCAR-T™ Platform

alfaCAR-T™ is an advanced CAR-T development platform focused on delivering potent and sustained cancer immunotherapies. By integrating state-of-the-art engineering, optimized antigen targeting, and proprietary enhancements for immune persistence, alfaCAR-T™ addresses many of the limitations commonly associated with traditional CAR-T approaches.

Key Parameter	Conventional CAR-T	alfaCAR-T™
Durability of Response	May wane over time, often requiring additional interventions	Engineered for extended anti-tumor activity, reducing relapse rates
Immune Memory Formation	Limited memory T cell generation, lower long-term surveillance	Enhanced T cell memory, providing sustained immunological vigilance
Tumor Microenvironment	Susceptible to immunosuppressive factors in solid tumors	Improved resilience in harsh tumor environments, boosting efficacy
Antigen Targeting	Standard scFv-based constructs with variable specificity	Optimized antigen-binding domains for high specificity and fewer off-target effects

alfaCAR-T™ platform is committed to expediting the discovery and optimization of CAR-T therapies, offering an integrated solution for preclinical immunotherapy research.

Antigen Discovery

Bioinformatics-Driven: In-depth computational analysis to identify the most promising tumor antigens.
Validation Pipelines: Rigorous in vitro and in vivo testing to confirm antigen relevance.

CAR Construct Design

Customizable Modules: scFv optimization, hinge region tuning, and signaling domain selection.
Durability-Focused Engineering: Enhancements aimed at sustaining T cell activity under hostile tumor conditions.

CAR-T Engineering & Cell Modification

Gene Editing: Advanced gene editing tools for precise modifications.
Viral & Non-Viral Delivery: Multiple delivery routes for flexible and efficient transduction.

Functional Testing & Characterization

Cytotoxicity Assays: Confirm anti-tumor potency.
Memory T Cell Profiling: Assess the longevity and reactivity of engineered cells.
In Vivo Efficacy Models: Validate performance in immunocompetent and immunodeficient models.

Comprehensive Quality Check

Preclinical-Grade Standards: Execute every stage of development under rigorous quality controls, meeting the demands of preclinical research.
High-Fidelity Results: Generate consistent and reproducible data to de-risk and accelerate your path to clinical translation.

Why Choose alfaCAR-T™?

Tailored Approach to CAR‑T Innovation

Every step is customized for optimal therapeutic outcomes.

Emphasis on Durability & Memory

Designed to enhance T-cell durability and reduce relapse.

Unparalleled Technical Expertise

Expert teams deliver cutting-edge solutions and research.

Contact Us

Partner with us to accelerate your CAR-T cell therapy development. Alfa Cytology provides tailored solutions that cover every stage of CAR-T engineering—from precise construct design and rigorous characterization to optimized production and quality assurance. Contact us today to discuss how our innovative CAR-T development services can help you overcome therapeutic hurdles.

Reference

Yang, Y. H., et al.; (2022). CAR-T Cell Therapy for Breast Cancer: From Basic Research to Clinical Application. International journal of biological sciences, 18(6), 2609-2626.

For research use only.

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As a pioneer in alfaCAR-T cell therapy development, Alfa Cytology delivers comprehensive preclinical solutions to advance next-generation cancer immunotherapies. Our integrated technology platform combines state-of-the-art alfaCAR-T^TM design capabilities with precision engineering and multi-dimensional characterization systems, accelerating translational research from concept to preclinical application. Through innovative targeting strategies and optimized construct development, we empower researchers to overcome key challenges in cellular therapy development and expedite the path to targeted cancer treatment.