Mutated epidermal growth factor receptor (EGF-RvlII) may provide a tumor-specific target for immunotherapy of breast carcinomas and a prognostic marker for the prediction of the clinical outcome of this malignancy. Among the known tumor-specific mutated proteins, EGF-RvlII is unique because it is expressed both on the surface and in the cytoplasm of malignant cells, rendering this molecule a potential therapeutic target for both B and T cells. Both arms of the immune system play an important role in the control of cancer growth. Our preliminary studies indicate that breast cancer patients raise humoral and cellular immune responses to EGF-RvlII expressed by their growing tumors. However, a significant correlation between these immune responses and EGF-RvlII expression by patients' tumors could not be established in that small study. Furthermore, it is not known whether the immune responses have any relationship with known prognostic breast cancer markers. The oncogenic potential of EGF-RvlII has been well established by in vitro transfection of tumor and normal cells with EGF-RvlII cDNA. However, it is not known whether EGF-RvlII expression by breast tumors confers increased aggressiveness in these tumors and poor outcomes in patients. Thus, we will determine: 1) Whether EGF-RvlII expression (mRNA, protein) by breast cancer patients' tumors is associated with the induction of EGF-RvlII-specific humoral and/or cellular immune responses in the patients' lymphocytes. 2) Whether the immune responses to EGF-RvlII have any relationship with known breast cancer prognostic markers, including patient age, tumor size and grade, lymph node involvement, and estrogen receptor, progesterone receptor, HER-2 and wild-type EGF-R status, and 3) Whether EGF-RvlII expression (mRNA, protein) by breast carcinomas has any relationship with known breast cancer prognostic markers. The proposed studies provide the rationale for specific active immunotherapy of breast carcinomas by targeting EGF-RvIII and will elucidate the potential of EGF-RvIII as a new prognostic marker for these tumors. ? ?

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
5R01CA090748-02
Application #
6735640
Study Section
Pathology B Study Section (PTHB)
Program Officer
Lively, Tracy (LUGO)
Project Start
2003-04-11
Project End
2006-03-31
Budget Start
2004-04-01
Budget End
2005-03-31
Support Year
2
Fiscal Year
2004
Total Cost
$255,949
Indirect Cost
Name
Wistar Institute
Department
Type
DUNS #
075524595
City
Philadelphia
State
PA
Country
United States
Zip Code
19104