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Project

Determinants of T-Cell Activity in Bladder Cancer

Funder: Congressionally Directed Medical Research Programs

Funding period
USD 549 K
Funding amount
Abstract
PUBLIC ABSTRACT

Bladder cancer is the fifth most common cancer in the US, and when metastatic or locally advanced, is highly lethal. Bladder cancer prevalence in military Veterans is two times higher than in the general population. Augmentation of the immune response with drugs referred to as checkpoint blockers leads to clinical responses and long-term disease control in a minority of patients with advanced bladder cancer. Based on encouraging Phase II trial data, the PD-L1 targeting checkpoint blocker atezolizumab was approved by the Food and Drug Administration in May 2016 for use in patients with advanced bladder cancer. While a landmark event given the lack of progress in the management of advanced bladder cancer over the previous decades, responses to atezolizumab by traditional criteria are observed in only about 15% of patients, indicating a strong need to develop methods to augment immune mediated tumor killing.



Dr. Arora has been an Assistant Professor in the Department of Internal Medicine, Division of Medical Oncology, Section of Molecular Oncology since July 2014. He is a physician-scientist that treats bladder cancer clinically and was the site Principal Investigator (PI) on a trial investigating checkpoint blockade in metastatic bladder cancer. With his previous basic science training and excellent mentorship, he is well positioned to develop a career at the forefront of bladder cancer and immunotherapy research. The goal of the PI is to improve the efficacy of checkpoint blockade in bladder cancer patients. His approach is to generate relevant mouse models of bladder cancer immunotherapy and then rigorously characterize them to understand what factors determine tumor sensitivity to the immune system, and what factors impair immune response. These insights will then be used to develop new approaches to treat bladder cancer in the clinic. The preliminary data suggest a possible mechanism that limits the effectiveness of checkpoint blockade in bladder cancer patients. In specific, it appears that bladder cancer cells release factors that suppress the immune response against bladder cancer. There are drugs already in development for other diseases that target this type of resistance mechanism. Thus, if the hypothesis is true, these drugs could be tested in bladder cancer patients within 1-2 years. Other novel strategies for enhancing immunotherapy may also emerge, as the proposed work illuminates barriers to immune rejection of bladder cancer.
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System

Categories
  • FOR (ANZSRC)

    1107 Immunology

  • FOR (ANZSRC)

    1112 Oncology and Carcinogenesis

  • RCDC

    Cancer

  • RCDC

    Clinical Research

  • RCDC

    Clinical Trials and Supportive Activities

  • RCDC

    Immunization

  • RCDC

    Urologic Diseases

  • RCDC

    Vaccine Related

  • HRCS HC

    Cancer

  • HRCS RAC

    5.1 Pharmaceuticals

  • Health Research Areas

    Biomedical

  • Broad Research Areas

    Basic Science