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Immunotherapy of human bladder cancer

人类膀胱癌的免疫治疗

基本信息

批准号：
8965456
负责人：
Lawrence Fong
金额：
$ 36.26万
依托单位：
UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
依托单位国家：
美国
项目类别：
财政年份：
2015
资助国家：
美国
起止时间：
2015-07-02 至 2020-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8965456
关键词：
Antibodies Antigens Antitumor Response Biological Assay Biological Markers Biopsy Bladder Bladder Neoplasm Blood Blood Circulation Calmette-Guerin Bacillus Cancer Patient Cell physiology Cells Cessation of life Cisplatin Clinical Clinical Research Clinical Trials Comorbidity Correlative Study Cystectomy Data Disease Drug Targeting Effectiveness Flow Cytometry Future Human Immune Immune response Immunity Immunologics Immunotherapeutic agent Immunotherapy In complete remission Individual Infiltration Laboratory Finding Lead Ligands Localized Disease Malignant Neoplasms Malignant neoplasm of urinary bladder Modality Muscle Neoadjuvant Therapy Neoplasm Metastasis Operative Surgical Procedures Organ Outcome Pathologic Patients Pharmaceutical Preparations Phase Phase I Clinical Trials Phase II Clinical Trials Proteins Radical Cystectomy Recruitment Activity Recurrence Refractory Relapse Relative (related person)Resected Retreatment Role Salvage Therapy San Francisco Site Surface T-Cell Receptor T-Lymphocyte Tissues Toxic effect Transitional Cell Carcinoma Tumor Tissue Work adaptive immunity base bladder transitional cell carcinoma cancer therapy chemotherapy density design high throughput screening immune activation improved intravesical malignant breast neoplasm next generation sequencing novel prevent programs public health relevance receptor response standard of care therapy development treatment effect tumor tumor microenvironment

项目摘要

DESCRIPTION (provided by applicant): Immunotherapy has emerged as an important treatment modality for cancer. In contrast to most other cancer treatments, immunotherapy can induce durable clinical response in metastatic disease. Antibodies targeting PD-1 and anti-PD-L1 have shown significant clinical activity in multiple diseases. Importantly, dramatic clinical responses have been seen in patients with the metastatic bladder, a disease in which no new drugs have been approved for over 20 years. The mechanism by which these immunotherapies work in cancer patients is unknown, nor are there robust biomarkers that predict of response to these treatments. We will perform a clinical study administering anti-PD-L1 antibody in patients with localized bladder cancer prior to these patients undergoing planned surgery for their cancer. We propose to study the effects of anti-PD-L1 antibody treatment not just in the blood but within the actual tumor. We will determine whether this immunotherapy increases the number of T cells into the tumor by examining tissues from biopsies obtained before treatment and from the bladder tumor resected following treatment. We will use next generation sequencing to track individual T cell clones in the blood and tumors to also determine whether T cells present in the tumor are being recruited to the tumor site or were already at the tumor. We will study how this treatment activates a systemic immune response. Understanding how these treatments work within patients, including at the level of the tumor tissue, will provide avenues t improve the efficacy of this approach and/or develop biomarkers to identify those patients that can benefit from treatment. Moreover, if significant tumor regression is seen, this treatment approach could transform our approach to localized bladder cancer. Finally, the clinical and laboratory findings derived from this trial may also help transform in how metastatic bladder cancer could be treated and contribute significantly to the design of future clinical trials with P-L1 and/or PD-1 targeted drugs.