Next generation immunotherapy solutions against macrophages to overcome cancer immuno-resistance

Monospecific antibody-based targeting of immune cells has revolutionized cancer immunotherapy, yet several patients remain resistant to these. Tumours with non-immunogenic profile (as opposed to immunogenic tumours), that are low in T cells and high in tumour associated macrophages (TAM) infiltration, dominate such immuno-resistance. Current approaches for immunotherapy are largely T cell focused, while these immune-resistant tumours are low in T cells. Therefore, targeting TAMs, needs to be prioritized for such tumours. Yet, initial clinical studies with anti-TAM monospecific antibodies have been largely unimpressive. We recently found a unique TAM subset, specifically enriched in non-immunogenic tumours that were resistant to monospecific antibodies targeting both T cells and TAMs. However, our translational data implied that these TAMs might be susceptible to hitherto non-existent multispecific antibodies. Thus, creation of such novel antibodies is the main objective of this proof-of-concept project. Such TAM targeting multispecific antibodies have high implications for intellectual property generation and socio-economic leverage, since patients with non-immunogenic tumours represent 71.6% of all cancer patients.

Keywords:Macrophages, Tumour immune-resistance, Multi-specific antibodies, Cancer immunotherapy, Reverse translation

Disciplines:Applied immunology, Cancer biology, Cancer therapy, Innate immunity