EGF-RvIII in Breast Cancer

描述（由申请人提供）：突变的表皮生长因子受体（EGF-RvII）可以为乳腺癌的免疫治疗提供肿瘤特异性靶点，并为预测这种恶性肿瘤的临床结局提供预后标志物。在已知的肿瘤特异性突变蛋白中，EGF-RvII II是独特的，因为它在恶性细胞的表面和细胞质中表达，使该分子成为B和T细胞的潜在治疗靶。免疫系统的两个分支在控制癌症生长中起着重要作用。我们的初步研究表明，乳腺癌患者的体液和细胞免疫应答EGF-RvII表达的肿瘤生长。然而，在该小型研究中不能建立这些免疫应答与患者肿瘤的EGF-RvII表达之间的显著相关性。此外，尚不清楚免疫应答是否与已知的预后乳腺癌标志物有任何关系。通过用EGF-RvII cDNA体外转染肿瘤和正常细胞，已经很好地建立了EGF-RvII的致癌潜力。然而，目前尚不清楚乳腺肿瘤的EGF-RvII表达是否会增加这些肿瘤的侵袭性和患者的不良结局。因此，我们将确定：1）乳腺癌患者肿瘤的EGF-RvII表达（mRNA、蛋白质）是否与患者淋巴细胞中EGF-RvII特异性体液和/或细胞免疫应答的诱导相关。2)对EGF-RvII的免疫应答是否与已知的乳腺癌预后标志物有任何关系，包括患者年龄、肿瘤大小和分级、淋巴结受累以及雌激素受体、孕激素受体、HER-2和野生型EGF-R状态，和3）乳腺癌的EGF-RvII表达（mRNA、蛋白质）是否与已知的乳腺癌预后标志物有任何关系。拟议的研究提供了通过靶向EGF-RvIII进行乳腺癌特异性主动免疫治疗的基本原理，并将阐明EGF-RvIII作为这些肿瘤的新预后标志物的潜力。

DESCRIPTION (provided by applicant): 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.