May 2022: Cancer Immunotherapy (CIMT) Annual Meeting – scientific poster
UPDATE: This poster received the CIMT 2022 Poster Award, Therapeutic Vaccines. Congratulations to all involved!
An agonistic CD40 bispecific antibody designed for flexible synthetic peptide-cargo delivery through an affinity interaction, a way to ensure optimal T cell activation
Ida Olsson 1,3, Aman Mebrahtu 2,3, Rosanne Veerman 3, Juan Astorga 4, Jimmy Ytterberg 1, Annika Lindqvist 1, Leif Dahllund 4, Anders Olsson 4, Oskar Andersson 4, Johan Rockberg 2,3, Helena Persson 2,4, Sara Mangsbo 1,3.
1Uppsala University, Uppsala, Sweden, 2Kungliga Tekniska Högskolan, Stockholm, Sweden, 3Strike Pharma AB, Uppsala, Sweden, 4Karolinska University, Stockholm, Sweden
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.
April 2022: American Association for Cancer Research, Annual Meeting, New Orleans – scientific poster
Development of an Adaptable Drug Affinity Conjugate, targeting the CD40 protein, provides a flexible therapeutic peptide cargo delivery to dendritic (APC) cells
Ida Laurén 1, Mohamed Eltahir 1,3, Aman Mebrahtu 2,3, Rosanne Veerman 3, Juan Astorga 4, Aljona Saleh 1, Jimmy Ytterberg 1, Annika Lindqvist 1, Leif Dahllund 4, Anders Olsson 4, Oskar Andersson 4, Johan Rockberg 2,3, Helena Persson 2,4, Sara Mangsbo 1,3.
1 Uppsala University, Uppsala, Sweden, 2 KTH Royal Institute of Technology, Stockholm, Sweden, 3 Strike Pharma AB, Uppsala, Sweden, 4 Karolinska University, Stockholm, Sweden
CD40 agonistic antibodies targeting antigen-presenting cells (APCs) rely on simultaneous presentation of an antigen for optimal efficacy since the co-stimulatory signal alone will not lead to T-cell activation. The ADAC technology platform utilizes a high-affinity interaction between a short non-immunogenic peptide-tag (pTag) and a single-chain fragment (scFv) of the antibody to enable attachment of the peptide cargo.
This poster demonstrates the ability of a novel Adaptable Drug Affinity Conjugate (ADAC) (a refinement of the traditional Antibody Drug Conjugate (ADC) approach) to improve peptide stability, while retaining agonistic activity and providing superior T-cell activation and expansion.
This first-in-class drug delivery strategy using ADAC technology meets demands for a flexible peptide cargo delivery strategy, ensuring in vivo T-cell priming via a CD40- targeted approach. Simultaneous immune activation and peptide presentation can ensure optimal drug efficacy and safety.