EGF-RvIII in Breast Cancer

描述(申请人提供)：突变的表皮生长因子受体(EGF-RvlII)可能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果提供预后标记物。在已知的肿瘤特异性突变蛋白中，EGF-RvlII是独一无二的，因为它既表达在肿瘤细胞的表面，也表达在细胞质中，使该分子成为B和T细胞的潜在治疗靶点。免疫系统的两只手臂在控制癌症生长方面都发挥着重要作用。我们的初步研究表明，乳腺癌患者提高了对其生长的肿瘤表达的EGF-RvlII的体液和细胞免疫反应。然而，在这项小型研究中，这些免疫反应与患者肿瘤组织的EGF-RvlII表达之间的显著相关性并不能得到证实。此外，目前尚不清楚免疫反应是否与已知的乳腺癌预后标志物有任何关系。用EGF-RvlII基因体外转染肿瘤细胞和正常细胞，证实了EGF-RvlII的致癌潜能。然而，目前尚不清楚乳腺肿瘤中EGF-RvlII的表达是否会增加这些肿瘤的侵袭性并降低患者的预后。因此，我们将确定：1)乳腺癌患者肿瘤中EGF-RvlII的表达(mRNA、蛋白)是否与患者淋巴细胞中EGF-RvlII特异性体液和/或细胞免疫反应的诱导有关。2)EGF-RvlII的免疫应答是否与已知的乳腺癌预后指标有关，包括患者年龄、肿瘤大小和分级、淋巴结转移、雌激素受体、孕激素受体、HER-2和野生型EGF-R状态；3)乳腺癌EGF-RvlII的表达(mRNA、蛋白)是否与已知的乳腺癌预后指标有关。这些研究为以EGF-RvIII为靶点的乳腺癌的特异性主动免疫治疗提供了理论基础，并将阐明EGF-RvIII作为乳腺癌新的预后标志物的潜力。

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.