Philip Greenberg, M.D.

Philip Greenberg, M.D.

Institution: Fred Hutchinson Cancer Research Center

Project: Overcoming obstacles for cellular immunotherapy against lung cancer

Grant(s): Lung Cancer Discovery Award

Immune checkpoint therapy (ICT), which enhances immune responses against tumors, has shown dramatic results in lung cancer; however, only half of patients benefit from this therapy. ICT relies on ‘re-awakening’ T cell responses against tumors, but only about 50% of patients have evidence of such pre-existing responses. Adoptive cell transfer (ACT), involving the engineering of patients’ T cells to recognize tumors, allows for generation of therapeutic anti-tumor responses. ACT for lung cancer faces unique barriers to sustaining functional immune responses, as well as potential toxic effects from therapy. We will clarify the requirements for safe eradication of lung cancer by ACT using a mouse model of lung cancer that closely mimics human disease. We will also identify and develop strategies to overcome hurdles to effective T cell responses that must be addressed for translation into treatment strategies to benefit lung cancer patients.

Update:

We are performing in-depth analyses of the mechanisms underpinning immunotherapy outcomes in sophisticated pre-clinical models and establishing the relevance of these systems to defined human patient subsets. We have profiled the lung tumor microenvironment in genetically engineered mouse models of lung cancer and human lung cancer to establish which therapeutically relevant patient disease subsets the models most closely recapitulate. We have begun to use our findings to experimentally probe the roles of specific suppressive factors common to mouse and human lung cancer on ACT outcomes, as well as pursuing therapeutic and engineering strategies to overcome them.

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