Departments of Obstetrics & Gynecology, OSU Wexner Medical Center, James Cancer Hospital & Solove Research Institute & the Comprehensive Cancer Center, The Ohio State University, Columbus, OH 43210, USA.
Future Oncol. 2012 Aug;8(8):961-87. doi: 10.2217/fon.12.95.
The ErbB family (HER-1, HER-2, HER-3 and HER-4) of receptor tyrosine kinases has been the focus of cancer immunotherapeutic strategies while antiangiogenic therapies have focused on VEGF and its receptors VEGFR-1 and VEGFR-2. Agents targeting receptor tyrosine kinases in oncology include therapeutic antibodies to receptor tyrosine kinase ligands or the receptors themselves, and small-molecule inhibitors. Many of the US FDA-approved therapies targeting HER-2 and VEGF exhibit unacceptable toxicities, and show problems of efficacy, development of resistance and unacceptable safety profiles that continue to hamper their clinical progress. The combination of different peptide vaccines and peptidomimetics targeting specific molecular pathways that are dysregulated in tumors may potentiate anticancer immune responses, bypass immune tolerance and circumvent resistance mechanisms. The focus of this review is to discuss efforts in our laboratory spanning two decades of rationally developing peptide vaccines and therapeutics for breast cancer. This review highlights the prospective benefit of a new, untapped category of therapies biologically targeted to EGF receptor (HER-1), HER-2 and VEGF with potential peptide 'blockbusters' that could lay the foundation of a new paradigm in cancer immunotherapy by creating clinical breakthroughs for safe and efficacious cancer cures.
表皮生长因子受体家族（HER-1、HER-2、HER-3 和 HER-4）的受体酪氨酸激酶一直是癌症免疫治疗策略的焦点，而抗血管生成疗法则集中在 VEGF 及其受体 VEGFR-1 和 VEGFR-2 上。肿瘤学中针对受体酪氨酸激酶的药物包括针对受体酪氨酸激酶配体或受体本身的治疗性抗体，以及小分子抑制剂。许多美国食品和药物管理局批准的针对 HER-2 和 VEGF 的疗法表现出不可接受的毒性，并且显示出疗效、耐药性发展和不可接受的安全性问题，这些问题继续阻碍它们的临床进展。针对肿瘤中失调的特定分子途径的不同肽疫苗和肽模拟物的联合应用可能增强抗肿瘤免疫反应，绕过免疫耐受并规避耐药机制。本文的重点是讨论我们实验室二十年来在合理开发用于乳腺癌的肽疫苗和治疗剂方面的努力。本文强调了针对表皮生长因子受体（HER-1）、HER-2 和 VEGF 的新型、未开发的生物靶向治疗类别具有潜在的肽“重磅炸弹”的预期益处，这些药物可能为癌症免疫疗法创造新的范例奠定基础，从而为安全有效的癌症治疗带来突破。
