Sanjeev Mariathasan leads the biomarker strategy for the Atezolizumab/Tecentriq franchise. He also co-leads the Oncology Reverse Translation group. The aim of this group is to derive mechanistic and therapeutically actionable insights from Roche’s extensive clinical database as well as to identify novel targets for the cancer immunotherapy pipeline. Examples of his research include (1) the revelation of TGFβ-mediated signaling in aiding exclusion of T cells in stromal tissues surrounding the tumors and the demonstration of reversing these effects leading to enhanced anti-tumor efficacy with anti-TGFβ and anti-PD-L1 mAb combination therapy in preclinical models (Mariathasan et al, Nature 2018); and (2) the use of ctDNA as an exploratory endpoint in a phase 3 adjuvant bladder cancer trial, the results of which have the potential to change treatment decision paradigms in early-stage bladder cancer and potentially other solid tumor types (Powles et al, Nature 2021).
Peripheral Biomarkers Guiding Cancer Immunotherapy
Ira Mellman, Genentech
Human cells have been successfully used as treatment for blood cancers for decades but translating the promise to cell-based treatment for solid tumors has been slow. The advent of gene-editing techniques such as CRISPR, coupled with advances in our understanding of immunology and optimization of growing, manufacturing, transporting, storing, and handling specialized biological samples and materials is transforming the cell therapy field. We will hear in this session about some of the most promising work in the field, as well as the challenges in overcoming resistance