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Modified HER-2 Tumor Antigens for Vaccination in Cancer

Award Information
Agency: Department of Health and Human Services
Branch: National Institutes of Health
Contract: 1R41CA106107-01
Agency Tracking Number: CA106107
Amount: $99,899.00
Phase: Phase I
Program: STTR
Solicitation Topic Code: N/A
Solicitation Number: N/A
Timeline
Solicitation Year: N/A
Award Year: 2004
Award Start Date (Proposal Award Date): N/A
Award End Date (Contract End Date): N/A
Small Business Information
L2 DIAGNOSTICS, LLC BOX 8175
NEW HAVEN, CT 94904
United States
DUNS: N/A
HUBZone Owned: No
Woman Owned: No
Socially and Economically Disadvantaged: No
Principal Investigator
 MARK MAMULA
 (203) 737-2840
 MARK.MAMULA@YALE.EDU
Business Contact
 MARTIN MATESSICH
Phone: (203) 737-1952
Email: MJMATT@IX.NETCOM.COM
Research Institution
N/A
Abstract

DESCRIPTION (provided by applicant): The proposed studies are aimed at developing a new tumor immunotherapy by using isoaspartyl-modified peptides to break immune tolerance to "self" tumor antigens on breast cancer cells. Most tumor antigens have been characterized as normal, non-mutated self-peptides, linking the concepts of autoimmunity with the development of tumor immunity. Previous studies demonstrated that vaccination with xenogenic peptide antigens could overcome immune tolerance. We hypothesize that isoaspartyl-modified peptides can activate tumor reactive immune responses that lead to tumor reduction or elimination. This hypothesis is supported by our preliminary studies using a murine model of autoimmunity. Immunization with isoaspartyl-modified peptides generated cytotoxic (killer) T cells and humoral immune responses to "self antigens." The proposed studies will extend these observations to a transgenic mouse model of mammary tumors. We will immunize neu transgenic mice with isoaspartyl-modified peptides representing selected epitopes in the oncogenic HER-2/neu "self" tumor antigen. We will then examine tumor-specific immune responses, tumor regression, and histology in this genetic mouse mammary tumor model that resembles human breast cancer. Our long-term goal is to develop an isoapartyl-modified peptide vaccine that will overcome immune tolerance in breast cancer patients, and enhance pre-existing immunity to HER-2/neu to therapeutic levels.

* Information listed above is at the time of submission. *

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