Interdisciplinary Initiatives Program Round 9 - 2018

Jennifer Cochran, Bioengineering
Julien Sage, Pediatrics and Genetics

The advent of drugs that invoke a patient's own immune system to attack tumors has changed the paradigm of cancer treatment and given new hope to patients. Although clinical successes are significant, the majority of patients do not respond to these first-generation therapies as the lack of active immune cells and the presence of inhibitory pathways in the tumor microenvironment hinder the anti-tumor immune response. To address these limitations we are using molecular engineering approaches, driven by deep biological insight, to develop a new class of immuno-therapeutics. Our approach targets a cell surface-expressed protein present on immune cells in the tumor microenvironment in over 90% of human non-small cell lung cancers (NSCLC); the presence of this protein causes immunotherapies to be ineffective. In the proposed project, we will create a novel drug candidate that can both: 1) ‘release the breaks’ that are holding the immune system back, as well as 2) ‘step on the gas’ to deliver an activation signal with the goal of converting inhibitory immune cells to stimulators. This interdisciplinary project marries the expertise of a bioengineer with a cancer biologist to develop an innovative therapeutic intervention for lung cancer, with the ultimate goal of clinical translation. The results generated here have broad reaching impact to other aggressive cancers, and will provide a foundation to enable others to develop drugs that leverage this targeted immune cell activation approach.