Exploiting the Unique T Cell Response to CMV for a Cancer Vaccine

Project: Research project

Description

DESCRIPTION (provided by applicant): The goal of this project is to develop an attenuated cytomegalovirus-based vaccine vector expressing the melanoma antigen trp-1 for use in tumor immunotherapy. Certain features of the immunobiology of CMV suggest that a vaccine based on it could make a unique contribution to the tumor immunotherapy arsenal. It is extraordinarily immunogenic for CD8 T cells;it has been shown to overcome self-tolerance to a tissue specific antigen, and as a vaccine vector it can be used sequentially. However, a live virus has obvious limitations as a vector for immune-compromised tumor patients. We have recently shown that a CMV vector that is completely replication deficient nevertheless establishes latency and can prime the characteristic ongoing massive immune response. The goal of the current project is to develop the replication deficient MCMV strain as a vaccine vector, using the well characterized B16 mouse melanoma model. The majority of the project is devoted to optimizing the immune response that can be elicited by the replication deficient vector. We will compare immunogenicity when the tumor antigen is expressed behind different viral promoters, and determine whether antigen expression and immunogenicity can be enhanced further by the use of adjuvants that drive viral IE gene expression. We will use two measures of vaccine efficacy (a) size of the CD8 T cell response an (b) ability to protect against tumor challenge using B16 cells. PUBLIC HEALTH RELEVANCE: Cytomegalovirus (CMV) infection, which is usually asymptomatic and has been safely used as a vaccine, generates a potent cellular immune response and immunological memory that is maintained for life. Previously, CMV has been engineered to induce the immune system to target normal tissues. Our goal is to harness this potent immune response elicited by CMV to test use as an effective tumor vaccine. A safe vaccine vector that is unable to replicate will be generated for this purpose.
StatusFinished
Effective start/end date4/1/093/31/11

Funding

  • National Institutes of Health: $167,845.00
  • National Institutes of Health: $201,725.00

Fingerprint

Cancer Vaccines
Cytomegalovirus
Vaccines
T-Lymphocytes
Immunotherapy
Cytomegalovirus Vaccines
Neoplasms
Immunologic Memory
Melanoma-Specific Antigens
Self Tolerance
Antigens
Attenuated Vaccines
Experimental Melanomas
Viral Genes
Cytomegalovirus Infections
Neoplasm Antigens
Cellular Immunity
Immune System
Viruses
Gene Expression

ASJC

  • Medicine(all)