Abstract B94: Efficacy of PD-1 - PD-L1 pathway disruptors in syngeneic models

Immune checkpoint modulators, such as antibodies targeting CTLA-4 or PD-1, are now being approved for treatment of patients with unresectable or metastatic melanoma and advanced squamous non-small cell lung cancer (NSCLC) who have progressed on or after platinum-based chemotherapy. Efficacy was also evidenced on other tumor types (renal cell carcinoma, bladder, Hodgkin lymphoma, colorectal carcinoma (CRC) ···). However, there is still needs to identify predictive biomarkers of response in order to select patients who will benefit from treatments. PD-L1 expression was proposed to be a good candidate for NSCLC, even if PD-L1 expression is a difficult parameter due to its expression on both tumor cells and immune cells as well as technical challenges to use immunohistochemical detection. The dynamic of the immune system as well as the site and time where interactions between tumor cells and immune cells take place, increase the complexity of having a solid biomarker identified. In addition, for other pathologies like colorectal carcinoma, genomic biomarkers were evidenced. For example, CRC patients with mismatch repair (MMR) deficiencies have an objective response rate of 62% compared with 0% in patients with MMR-proficient tumors.We propose here the use of syngeneic models to address mechanism of action and biomarker related questions for agent targeting PD-1 / PD-L1 axis. Syngeneic model systems remain one of the only options to analyse physiologically rel...
Source: Molecular Cancer Therapeutics - Category: Cancer & Oncology Authors: Tags: Immune Checkpoints: Poster Presentations - Proffered Abstracts Source Type: research