Ludwig Cancer Research and Agenus Inc. announced that the companies are advancing three selected monoclonal antibody checkpoint modulators (CPMs) into preclinical development. Agenus plans to develop the CPMs into single agents and in optimized combinations including possible combinations with anti-cancer vaccine and other agents.
The CPMs are part of Agenus’ recent acquisition of 4-Antibody AG. The selected product candidates include two GITR agonists and a CTLA-4 antagonist which target cell-surface checkpoint proteins that regulate immune responses. Robert Stein, chief scientific officer of Agenus, said “GITR, a checkpoint protein on T-lymphocytes, plays an important role in amplifying specific cellular immune responses, including those against tumors. We are encouraged to have identified high-quality agonist antibodies for this very competitive target, something that has proven difficult for many other companies. Furthermore, it is rational to combine CPMs such as CTLA-4 and PD-1 antagonists with anti-cancer vaccines, and we are collaborating on an on-going Phase 2 trial exploring Prophage and Yervoy (CTLA-4 antagonist) in patients with metastatic melanoma. Intelligently designed translational studies may improve the odds of success for our CPMs and accelerate their clinical development.”
CPMs such as CTLA-4 and PD-1 antagonists cause cancer to be more vulnerable to immune attack through neutralization of cancer cell defense while releasing anti-cancer immune response. Cancer vaccines improve the immune system’s recognition of cancer cells based on the mutant proteins they display. The two strategies are expected to deliver a potent combination against cancer.
Ludwig Cancer Research has collaborated with 4-Antibody AG for several years to develop the CPM products. Jonathan Skipper, Ludwig’s executive director of technology development, said “The collaboration with 4-Antibody allowed us to rapidly advance antibodies into development. We are now planning clinical studies to evaluate novel combinations of these antibodies. Ludwig has been at the forefront of translational research in immuno-oncology for several decades. Our ongoing relationship with Agenus is a good example of our broader strategy to advance cancer therapy.”