Scientific poster: Cancer Immunotherapy (CIMT) Annual Meeting 2022

An agonistic CD40 bispecific antibody designed for flexible synthetic peptide-cargo delivery through an affinity interaction, a way to ensure optimal T cell activation

For efficient tumor recognition, CD8 T-cells rely on antigen presentation and costimulation performed by antigen presenting cells (APCs). Agonistic CD40 antibodies support the activation of APCs, leading to increased activation and antigen presentation. However, monotherapy of agonistic CD40 antibodies has failed to generate clinical effect, possibly due to the failure to account for the importance of antigen-presentation for efficient T cell activation.

This poster shows the use of ADAC technology in the development of a novel anti-CD40 antibody clone, STRIKE-1001, as a cancer-treatment vaccine candidate. The ADAC technology enables cargo-delivery via a non-covalent high-affinity interaction between a scFv (single-chain variable fragments fused recombinantly to the parental antibody, in this case the anti-CD40 antibody) and a peptide tag (pTag) enabling the agonistic CD40 antibody to deliver an antigen-related peptide cargo to APCs while maintaining a more flexible approach of cargo delivery compared to a traditional antibody drug conjugate (ADC).

Using phage display, STRIKE-1001 was generated and agonistic activity was confirmed. After adaptation to the bispecific format, STRIKE 2001, this selected clone shows developability characteristics on par with the parental antibody, retained agonistic activity on human dendritic cells and improved CD8+ and CD4+ T-cell proliferation in vivo.

 

Please contact our Chief Scientific Officer, Associate Professor Sara Mangsbo, if you would like more information.

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