Therapeutic targeting of hypoxia inducible factors to augment anti-cancer antibody immunotherapy

Hypoxia is a common hallmark of human tumours. Rapid tumour cell proliferation, elevated energy demand, and an abnormal vasculature combine to deplete local O2. Consequently, substantial cellular adaptations are required to ensure survival within these harsh environments. Hypoxia-inducible factors (HIF) facilitate this process through altering transcription and enhancing tumour survival, angiogenesis, and metabolic reprogramming. However, these HIF-dependent effects also trigger recruitment/differentiation of immunosuppressive immune populations, restriction of immune cell infiltration, and restrained T-/NK-cell effector function. Consequently, hypoxic regions demonstrate profound immunosuppression and limited anti-tumour immunity. In this project, Garima will work at the cutting-edge of tumour immunology and drug discovery. Through industrial placement, Garima will receive training in advanced drug discovery platforms and contribute to potentially paradigm shifting first-in class drug development. Within the Antibody & Vaccine group, she will receive training in antibody effector assays, antibody engineering, in vivo tumour modelling techniques, and RNA sequencing data analytics.