Please enable JavaScript or talk to your local administrator to get JavaScript enabled.

Project

Intravesical Chitosan/IL-12 Immunotherapy for Bladder Carcinoma

Funder: National Cancer Institute

Funding period
USD 417 K
Funding amount
Abstract
Project Summary Bladder cancer is the sixth most common cancer diagnosis in the U.S. Although three-quarters of patients are diagnosed early with superficial (non-invasive) disease, bladder cancer is highly recurrent and requires long-term maintenance therapy and costly continuous surveillance. Novel therapies, capable of inducing durable anti-tumor responses, are needed to limit progressive recurrence and to improve survival. Immune-based therapies have demonstrated the potential to elicit, durable tumor-specific immunity. In particular, the pro-inflammatory cytokine, interleukin-12 (IL-12), has demonstrated remarkable anti-tumor activity and protective immunity in numerous preclinical tumor models. Previous research has demonstrated that chitosan, a natural polysaccharide derived from the exoskelatons of crustaceans, can enhance the anti- tumor efficacy of intravesically administered IL-12. Co-formulations of chitosan solution and IL-12 (chitosan/IL- 12) were found to eliminate established orthotopic bladder tumors and generate systemic tumor-specific protective immunity. The proposed project will continue the preclinical development of intravesical chitosan/IL-12 immunotherapy. Three independent aims are proposed. Aim 1 is designed to elucidate the mechanisms by which chitosan facilitates intravesical IL-12 delivery. Aim 2 will assess the pharmacokinetics, safety and tolerability of intravesical chitosan/IL-12 immunotherapy using clinically relevant endpoints. Aim 3 will begin to describe how an intravesical immunotherapy can generate systemic protective immunity. The overall goal of this project is to improve our mechanistic understanding of chitosan-enhanced intravesical delivery while providing critical preclinical data in support of translation of a promising new immunotherapy for the treatment of bladder cancer. At the same time, this project will enhance the biomedical research capacity at an AREA institution, provide valuable research opportunities for 2 new graduate students and expose approximately 15-25 undergraduate students to biomedical research.
Similar projects All >
Sorted by: Start Date
Project list item
Intravesical delivery of an Fc-enhanced CD40 agonist antibody for the treatment of bladder cancer

Bladder Cancer Advocacy Network to Jeffrey Ravetch, David Knorr

USD 300,000
2020 - 2022
Project list item
Recombinant CCL2 as a novel treatment strategy for bladder cancer

Bladder Cancer Advocacy Network to Neelam Mukherjee, Robert Scott Svatek

USD 50,000
2020 - 2021
Project list item
Targeting regulatory B cells (Bregs) to improve anti-bladder cancer immunity

Bladder Cancer Advocacy Network to Burles Avner Johnson, David McConkey

USD 50,000
2020 - 2021
Project list item
CD40 agonism for the treatment of bladder cancer

National Cancer Institute to CHRISTOPHER STUART GARRIS

USD 64,554
2020 - 2023
Project list item
Roles of epigenetic regulators in bladder cancer progression

University of California - Cancer Research Coordinating Committee to Zhu Wang

USD 74,960
2020 - 2020

System

Categories
  • FOR (ANZSRC)

    1107 Immunology

  • RCDC

    Cancer

  • RCDC

    Immunization

  • RCDC

    Urologic Diseases

  • RCDC

    Vaccine Related

  • HRCS HC

    Cancer

  • HRCS RAC

    5.1 Pharmaceuticals

  • Health Research Areas

    Biomedical

  • Broad Research Areas

    Clinical Medicine and Science