FR806 Fusion Switch CAR Construction Service

CAR-T-based cell has been demonstrated to be a promising therapy in the treatment of many different tumor types, especially in the treatment of relapsed or refractory B-cell malignancies. However, the administration of CAR-T cells is associated with serious adverse events, which can be fatal in some cases. Fatal off-target tumor toxicity and fatal cytokine release syndrome (CRS) have been reported in clinical trials. The combination of endogenous safety switches represents a reasonable strategy to control toxicity after adoptive T cell therapy. An ideal safety switch should be able to deplete transferred T cells with minimal damage to normal tissues. To minimize the toxicity to healthy tissues, foreign epitopes can be introduced into CAR-T cells for selective ADC targeting.

The 806 epitope of cryptic is one such candidate site because it is only exposed due to overexpression of EGFR or truncation of the extracellular domain. Creative Biolabs has developed a novel switch CAR - the fusion receptor by engineering the 806 recessive epitope of human epidermal growth factor receptor (EGFR) into the N-terminus of full-length human folate receptor 1 (FOLR1) (called FR806). The expression of FR806 allows the transduced T cells to be targeted by CH12, which is a monoclonal antibody that recognizes the 806 epitope in healthy tissues but cannot recognize wild-type EGFR. Therefore, FR806 constitutes a specific cell surface marker that eliminates transduced T cells.

Design of FR806

FOLR1 is a glycosylphosphatidylinositol (GPI)-linked membrane glycoprotein that mediates the uptake of folate into cells. Its effective endocytosis makes FOLR1 an important target for drug delivery to FOLR1-positive tumor cells. Data have shown that FR806 epitope and FOLR1 generated fusion receptor - FR806, which can mediate the internalization of ADC to eliminate FR806-expressing T cells. The selectivity of the 806 epitope and the internalization ability of FOLR1 make FR806 an efficient safety switch, which can be additionally used as a biomarker for detection and purification of human T cell immunotherapy.

The 806 epitope of EGFR was directly fused to the N-terminus of the full-length human FOLR1 gene. For easy detection, FR806 was co-expressed with EGFR via self-cleavage/ribosome skipping F2A peptide.

Creative Biolabs' FR806 Fusion Switch CAR Construction Service

Creative Biolabs offers specialized construction services to seamlessly integrate advanced safety features into your custom CAR-T constructs, dramatically improving the therapeutic index for your cell therapy candidates.

• Toxicity Mitigation Design: FR806 fusion receptor engineered by fusing the EGFR 806 epitope to full-length FOLR1, recognized by CH12 mAb for safety switch activation.
• On-Demand T Cell Depletion: Engineered CAR-T cells expressing FR806 are selectively targeted by an antibody-drug conjugate (ADC), with FOLR1-mediated internalization enabling regulated therapy termination to resolve CRS.
• Biomarker Integration: FR806 serves as a dual-function biomarker for transduced T cell detection/purification during manufacturing, ensuring product quality/homogeneity.
• Custom CAR Backbone Construction: Comprehensive design/build services for full CAR structures, including target scFv generation, co-stimulatory domain optimization (4-1BB/CD28), and signaling domain selection.

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What we can offer

Creative Biolabs provides an integrated suite of services for the design, construction, and preclinical validation of next-generation, controllable CAR-T cells, leveraging multiple innovative platforms to enhance both safety and efficacy.

Service Workflow

Our comprehensive service guides your project from initial design to final validated product, optimized for safety and efficacy.

Key Benefits

• Validated Safety Control: The FR806 switch is strategically designed using the EGFR 806 epitope, which is only recessively exposed due to overexpression or truncation of EGFR, preventing the safety switch itself from being a significant off-target risk in healthy tissue.
• Dual-Function Design: The integrated FOLR1 component actively mediates endocytosis, ensuring the efficient internalization and depletion of the CAR-T cell when targeted by an ADC.
• Streamlined Manufacturing: The FR806 construct is also an excellent surface biomarker, allowing for robust and easy detection, sorting, and quality control during T cell manufacturing.

FAQs

Why Choose Us?

The FR806 fusion switch CAR construction service from Creative Biolabs is essential for researchers and companies seeking to develop safer, more controllable, and ultimately more clinically viable CAR-T therapeutics. By expertly integrating the dual-function FR806 safety switch, we provide the control mechanism necessary to manage severe toxicity and advance high-potential candidates through the development pipeline.

Our team of cell therapy experts is ready to discuss your project's unique safety and design requirements. Partner with Creative Biolabs to engineer the future of controllable immunotherapy. Contact our team for more information and to discuss your project.

One-stop CAR Development Services

With state-of-art CAR development platform and advanced technologies, Creative Biolabs is capable of offering CAR-T-cell development service. For the regular or custom next-generation CAR construction, please refer to our related services: CAR Design & Construction. To further assess your switch CAR biological efficacy (e.g., cytokine production, tumor killing, and CAR-T cell proliferation), our scientists can also provide comprehensive downstream services to complete your whole research. Please click: CAR Cell In Vitro Assay Service, CAR-T Preclinical In Vivo Assay for more details.

CAR biomarker identification & selection High affinity scFv generation CAR design & construction Virus packaging & CAR transfection CAR in vitro assay CAR pre-clinical in vivo assay CAR clinical trial

Fig.1 One-stop CAR-T therapy development process.

For more detailed information, please feel free to contact us or directly sent us an inquiry.