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Combination immuno and metabolic therapy for early-stage lung adenocarcinoma

Institution: University of California, Los Angeles
Investigator(s): Claudio Scafoglio,
Award Cycle: 2019 (Cycle 29) Grant #: T29IP0694 Award: $499,756
Subject Area: Cancer
Award Type: High Impact Pilot Award

Initial Award Abstract
Lung cancer is the leading cause of cancer-related death worldwide. Despite the recent successes obtained in the treatment of advanced lung cancer with immunotherapy, the responses are usually limited in time. In order to improve the response to immunotherapy, we propose to follow two approaches: 1) start immunotherapy at an early stage, when the immune response did not reach exhaustion and the chances of success are higher; 2) administer combination treatments that potentiate immune therapy. A novel approach in the treatment of cancer consists in interfering with the sugar supply in the tumor. Cancers require sugar (glucose) to grow; glucose cannot freely enter the tumor cells but needs to be transported by specific proteins that shuttle the sugar inside the cells. We found out that the transporter expressed in early-stage adenocarcinoma, named SGLT2, is different for the glucose transporter expressed in immune cells. Drugs that block the SGLT2-dependent glucose transport have recently been FDA-approved for diabetes; we have shown that SGLT2 inhibitors can also delay the development of lung adenocarcinoma in pre-clinical studies. We also found that SGLT2 inhibitors increase the number of immune cells that are found in the tumors, suggesting that the inhibition of glucose uptake in the cancer cells may enhance the immune response against the tumor, probably by increasing the amount of glucose that is available in the tumor for the immune cells to proliferate and to mount an effective immune response. Therefore, we predict that SGLT2 inhibition will also make the tumors more responsive to immune therapy. In this project, we are going to 1) characterize the effects of metabolic treatment with SGLT2 inhibitors on the immune response against cancer in pre-clinical models; 2) evaluate the effect of combination treatment with SGLT2 inhibitors + immunotherapy. Both SGLT2 inhibitors and immunotherapy drugs have been approved by the FDA. Therefore, the proposed research has the potential to lead to the discovery and the quick clinical translation of a new combination treatment for lung adenocarcinoma.