Vaccines to Mobilize B Cells for Cancer

Background

Monoclonal antibodies are the primary treatment option for targeted cancer therapies, yet they pose significant limitations within the clinic. Current antibodies target surface markers that are present on both cancer and healthy cells triggering off-target effects following administration. Consequently, almost all monoclonal antibodies cause adverse reactions ranging from minor to severe (grade 3 or higher) responses and at times, treatment-induced deaths. By contrast, cancer cells possess unique markers in the form of mutated proteins that are located intracellularly and are absent within healthy cells. The fragments of these proteins are present on the cancer cells’ surface as peptides that are displayed on their major histocompatibility complex 1 (MHCI) molecules. For antibody therapies the capacity to target these peptide MHCI molecules would significantly mitigate off-target effects, resulting in a safer therapy.

Technology Overview

This technology from the University of Toronto is a vaccine that induces patients’ own B cells to produce antibodies that target cancer exclusive peptide MHCI molecules. Specifically, researchers have developed an antigen design that efficiently delivers a single-chain cancer peptide-MHCI (pMHCI) molecule to the lymph node (). This antigen design uniquely triggers the production of peptide MHCI targeting antibodies from B cells while traditional antigens (i.e. peptides or whole protein from which the peptides are derived from) fail to do so. The antigens can be delivered through multiple vaccine modalities such as recombinant proteins or encoded in mRNA. Overall, this vaccine platform induces continuous production of cancer exclusive antibodies directly within patients.

Stage of Development

Proof-of-concept studies have been conducted. The researchers have developed and characterized the antigen through in vitro assays. They have also verified that this antigen can induce specialized antibodies that recognize peptide MHCI molecules within a mouse model. Moreover, vaccination with this antigen protects against a melanoma challenge in prophylactic () and active therapy settings. Currently, they are conducting more in-depth analyses of the antibody response as well as evaluating the vaccine’s efficacy in treating existing tumors.

Benefits

This vaccine is a disruptive platform that, for the first time, mobilizes B cells towards effective cancer therapy. By placing the onus onto B cells to discover and mass produce antibodies, the vaccine overcomes several limitations associated with monoclonal antibody R&D and production. It offers personalization potential; its modular design allows incorporation of multiple patient-specific neoantigens.

Applications

The vaccine is intended to be used for cancer therapies as a form of targeted treatment option.