HapImmune™ platform

Aethon’s HapImmune™ platform: The convergence of targeted and immune therapy

The Aethon HapImmune platform, exclusively licensed to Aethon Therapeutics, is based on the novel observation by NYU researchers that when covalent inhibitors bind target proteins such as EGFR and RAS, they create drug-target peptide conjugates, called haptens, that can be presented by major histocompatibility complex (MHC), also known as human leucocyte antigen (HLA), molecules on the surface of tumor cells. In broadest terms, HapImmune is a mechanism to increase the antigenicity of any cancer-specific protein that can be targeted with any covalent drug and presented on HLA.

HapImmune uses NYU Langone Health’s proprietary repertoire of 100 billion synthetic antibody sequences to find antibodies that recognize drug-peptide complexes (haptens) presented by MHC molecules while avoiding binding to wild-type (e.g., drug-free) peptides on the same MHCs or to the free drug.

These antibodies are then reformatted into customized HapImmune bi-specific T cell engagers, with one recognition arm directed towards the drug-peptide:HLA and another towards anti-CD3 and/or other T cell surface proteins to recruit cytotoxic T cells. In vitro studies have shown that such molecules can selectively kill drug-treated cells–the resistant tumor cells–and do not bind the hapten alone except in the context of MHC/HLA.

Publications

23 May 2024, PNAS (Research Article),
Molecular basis for antibody recognition of multiple drug–peptide/MHC complexes

9 January 2023, Cancer Discovery (Research Article),
Creating MHC-Restricted Neoantigens with Covalent Inhibitors That Can Be Targeted by Immune Therapy

9 January 2023, Cancer Discovery (Commentary),
Convergence of Targeted and Immune Therapies for the Treatment of Oncogene-driven Cancers

Antibodies produced via the HapImmune platform are designed to activate T cells that will specifically kill tumor cells.