Peptide-Centric CAR Construction Service

The Importance of Peptide-centric CAR

Despite having obvious therapeutic effects on leukemias, the limited availability of tumor-specific membrane proteins for solid tumor killing limits CAR-T cell therapy. The Peptide-Centric Chimeric Antigen Receptor (PC-CAR) is a novel type of CAR that can detect oncoprotein epitopes displayed on the cell surface by HLAs. Scientists have developed a PC-CAR that targets the neuroblastoma-associated PHOX2B peptide. This makes it easier to kill tumor cells that share two common HLA allotypes. Therefore, peptide-centric CAR construction exhibits a promising strategy to expand CAR-T cell therapy for solid tumors and other types of cancer.

Fig. 1 PC-CARs targeting neuroblastoma's oncogenic peptide.¹

Key Advantages of PC-CAR for Targeting MHC Peptides Compared to TCR

• Wider targeting scope: PC-CAR can effectively target mutated oncoproteins.
• Superior peptide selectivity: PC-CAR can be characterized by superior peptide selectivity owing to its freedom from germline-encoded CDR1 and CDR2 constraints.
• Expander clinical research: Based on the second point, PC-CAR can target a peptide presented by multiple HLA alleles.

Our Peptide-centric CAR Construction Services: Comprehensive! Fast! Excellent!

Creative Biolabs has developed and widely provides peptide-centric CAR construction services for global customers to aid in your drug development projects. We can design specific PC-CARs targeting tumor-associated proteins according to the diverse needs of customers. Specifically, we provide well-developed several platforms for global customers to screen the appropriate scFv and can customize our service if you have desirable targets. In addition, we also deliver other types of CAR construction services (Leucine Zipper (SUPRA) CAR, Anti-FITC CAR, Convertible CAR, etc.) to support your projects. At Creative Biolabs, we provide full-around peptide-centric CAR construction services ranging from design to evaluation to enable your projects to run smoothly.

Fig. 2 Workflow of CAR construction services.

Representative Data

The unmutated peptide QYNPIRTTF, which is expressed on HLA-A*24:02, piqued the researchers' curiosity. This peptide is derived from PHOX2B, a neuroblastoma-dependent gene and master transcriptional regulator. Using anticipated possibly cross-reactive peptides, researchers developed peptide-centered chimeric antigen receptors (PC-CARs) by a strategy known as "counter-panning." These results suggest that PC-CARs might be able to add non-immunogenic intracellular oncoproteins to the list of immunotherapy targets. This means that additional HLA isotypes might be exploited for therapeutic targeting.

Fig.3 Tumor killing and breakthrough induced by PHOX2B-specific PC-CAR T cells.²

As a leader in immunotherapy development, Creative Biolabs strives to provide CAR construction services to aid in drug development for cancer therapy. If you are interested in our peptide-centric CAR construction services, please contact us for more details at your convenience.

References

1. Irving, Melita, et al. "A roadmap for driving CAR T cells toward the oncogenic immunopeptidome." Cancer Cell 40.1 (2022): 20-22.
2. Yarmarkovich, Mark, et al. "Cross-HLA targeting of intracellular oncoproteins with peptide-centric CARs." Nature 599.7885 (2021): 477-484.