Veterinary Chimeric Antigen Receptor Engineering

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Veterinary Chimeric Antigen Receptor Engineering

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Chimeric Antigen Receptor Structural Components Veterinary CAR Therapy Biomarker Identification Single-chain Variable Fragment (scFv) Expression In Vitro Assays for Veterinary CAR Therapy Why Choose Us?

Immune system cells such as T cells, NK cells, NKT cells, as well as macrophages, are modified to express chimeric antigen receptors (CARs) to recognize better and eliminate cancerous cells. Chimeric antigen receptor T cells (CAR T cells) have achieved remarkable success in the field of cancer tumor immunotherapy. CAR T cell therapy has gained great success, especially in hematological malignancies. The engineered T cell receptors, known as CARs, are comprised of three parts: an extracellular single-chain variable fragment (scFv), which is straightened against a recognizable antigen, a transmembrane domain, and the intracytoplasmic activating domain. With a profound understanding of CAR structure and function, BioVenic has launched a variety of Veterinary Chimeric Antigen Receptor Engineering-related technical services. Through the rational design of the scFv domain, hinge domain, transmembrane domain, and intracellular domain, advanced gene editing technology, and high-throughput detection platform for multiple animal targets, we help researchers in the field of veterinary cell therapy solve various problems encountered in their research.

Fig.1 Different Regulatory Components of Chimeric Antigen Receptor (CAR) T cells (Dwivedi, et al., 2019) Fig.1 Schematic Representation of Different Regulatory Components of Chimeric Antigen Receptor (CAR) T cells.^1,2

Chimeric Antigen Receptor Structural Components

Typical CARs are engineered structures consisting of an extracellular antigen recognition domain connected to transmembrane and intracellular domains and may include spacer regions.

The Extracellular Antigen Recognition Domain	Generally consists of a scFv derived from the heavy and light chain variable regions of a tumor-associated antigen (TAA)-specific monoclonal antibody. The scFv domain's targets can include proteins, peptide antigens, and surface marker molecules, extending to glycoproteins, glycolipids, and gangliosides that are uniquely expressed on tumor cells.
Extracellular Spacer Region	If present, it is located between the extracellular targeting moiety and the transmembrane domain. It plays a crucial role in ensuring the proper positioning of the antigen-binding domain during the TAA-CAR interaction. By adjusting the distance of the target epitope binding site from the cell membrane, the CAR signal strength can be modulated.
Transmembrane Domain	Derived from type I membrane proteins such as CD3, CD4, CD8, and CD28. Mutations in the transmembrane domain can result in a decreased functional capacity of the CAR to respond to its antigen.
Intracellular Domain	Includes cytoplasmic signaling domains sourced from a CD3ζ chain, the γ or ε signaling components of an Fc receptor, and co-stimulatory molecules like CD28, as well as members of the tumor necrosis factor (TNF) receptor family. The costimulatory domain enables the dual activation of costimulatory molecules and intracellular signals, allowing T cells to continuously proliferate and release cytokines, thereby enhancing the antitumor capabilities of the T cells. The Signaling Domain functions in T-cell signal transduction.

Veterinary CAR Therapy Biomarker Identification

Different CAR design strategies are usually required for different tumor targets. BioVenic possesses advanced platforms for proteomics, metabolomics, and multi-omics detection and analysis. These platforms can provide valuable insights into target screening strategies in the development of veterinary CAR therapies and CAR design. By detecting and analyzing tumor antigens expressed in samples from various organs and tissues, we assist scientists in exploring new potential tumor targets for subsequent CAR design and therapeutic development.

Single-chain Variable Fragment (scFv) Expression

The single-chain variable fragment (scFv) is composed of the heavy chain variable domain (VH) and the light chain variable domain (VL) of an antibody, connected by a flexible short peptide linker consisting of 10-25 amino acids. It has been demonstrated that reducing the affinity of scFv can enhance selective recognition of tumors, thereby decreasing toxicity to both the target and non-tumorous areas. We possess advanced gene editing and recombinant antibody expression platforms, enabling the expression of desired antibody fragments in various expression systems. Through the construction, screening, and expression of an scFv library, BioVenic provides efficient solutions for research related to the development of veterinary CAR-related therapies.

In Vitro Assays for Veterinary CAR Therapy

A rational CAR design is the foundation for constructing an efficient CAR therapy. By conducting in vitro experiments to assess cytotoxic activity, cytotoxic specificity, cell proliferation capacity, and cytokine secretion ability, researchers can perform preliminary evaluation and screening of CAR-related cell therapy efficacy. With our in vitro CAR therapy evaluation platform, researchers can perform diverse assessments of veterinary CAR therapy efficacy, which not only reflects the effectiveness of the CAR design but also provides a basis for subsequent therapy development.

Why Choose Us?

Extensive Project Experience

Through careful evaluation of research projects, we provide assistance on critical issues in the development of veterinary CAR therapies.

Customized Solutions

For different targets and disease types, our solutions are specifically tailored to address the challenges in the development of veterinary CAR therapies.

Multiple Experimental Services

Our veterinary biomarker discovery platform, antibody design and expression platform, and in vitro efficacy evaluation platform offer researchers comprehensive support at every stage of veterinary CAR therapy development.

The development of veterinary CAR therapies offers valuable opportunities for curing animal diseases. With a profound understanding of CAR structures and continuous learning of research frontiers, BioVenic's expert team can provide customized services for veterinary CAR design. We offer a range of advanced services including the discovery of targets for veterinary CAR therapy, CAR design and expression as well as in vitro evaluation of veterinary CAR therapies. if you have research needs for the development of veterinary CAR therapy and CAR design, please feel free to contact us. We will assess your specific requirements and provide tailored solutions.

References

Image retrieved from Figure 1 "Schematic representation of different regulatory components of Chimeric Antigen Receptor (CAR) T cells." Dwivedi et al., 2019, used under [CC BY 4.0] (https://creativecommons.org/licenses/by/4.0/). Without modification.
Dwivedi, Alka, et al. "Lymphocytes in cellular therapy: functional regulation of CAR T cells." Frontiers in immunology 9 (2019): 3180.