Early Drug Development for Innovative Therapies Division, European Institute of Oncology, Via Ripamonti 435, 20141 Milano, Italy.
Breast. 2013 Aug;22 Suppl 2:S96-9. doi: 10.1016/j.breast.2013.07.018.
INTRODUCTION: Evading immune destruction is an emerging hallmark of cancer. Immunotherapy of cancer is categorized as either specific stimulation of the immune system by active immunization, with cancer vaccines, or passive transfer of humor or cellular materials, such as, tumor specific antibodies (including immunomodulators) or adoptive cell therapy that inhibit the function of- or directly kill tumor cells. Modulation of immune response in cancer patients is the result of a balanced activity of T regulators and T effector cells. METHODS AND RESULTS: We will present the current information and the prospects for the future of immunotherapy in patients with breast cancer including tumor antigens for vaccines and targets for monoclonal antibodies and adoptive T-cell therapy. DISCUSSION: Active immunotherapy in breast cancer and its implementation into clinical trials has largely been a frustrating experience in the last decades. After many years of controversy, the concept that the immune system regulates cancer development is experiencing a new resurgence. It is clear that the cancer immunosurveillance process indeed exists and potentially acts as an extrinsic tumor suppressor. It has been also clear that the immune system can facilitate tumor progression by sculpting the immunogenic phenotype of tumors as they develop. Cancer immunoediting represents a refinement of the cancer immunosurveillance hypothesis and resumes the complex interaction between tumor and immune system into three phases: elimination, equilibrium, and escape. CONCLUSION: What do we know about tumor immunogenicity and how might we therapeutically improve tumor immunogenicity? The first vaccine and the first immunomodulating agent were recently approved by the US Food and Drug Administration (FDA) for the treatment of prostate cancer (sipuleucel-T) and melanoma (ipilimumab), respectively. The success of future immunotherapy strategies will depend on the identification of additional immunogenic antigens that can serve as the best tumor-rejection targets. Therapeutic success will depend on developing the best antigen delivery systems and on the elucidation of the entire network of immune signalingsignaling pathways that regulate immune responses in the tumor microenvironment.
简介:逃避免疫破坏是癌症的一个新出现的特征。癌症的免疫疗法可分为通过主动免疫用癌症疫苗特异性刺激免疫系统,或被动转移体液或细胞物质,如肿瘤特异性抗体(包括免疫调节剂)或过继细胞疗法,从而抑制肿瘤细胞的功能或直接杀死肿瘤细胞。癌症患者免疫反应的调节是 T 调节细胞和 T 效应细胞平衡活性的结果。
方法和结果:我们将介绍目前乳腺癌免疫治疗的信息和未来前景,包括疫苗用肿瘤抗原和单克隆抗体及过继 T 细胞治疗的靶点。
讨论:在过去几十年中,乳腺癌的主动免疫疗法及其临床试验的实施在很大程度上是令人沮丧的经历。经过多年的争议,免疫系统调节癌症发展的概念正在经历新的复兴。很明显,癌症免疫监视过程确实存在,并可能作为外在的肿瘤抑制因子发挥作用。同样清楚的是,免疫系统可以通过塑造肿瘤的免疫原性表型来促进肿瘤的进展,因为它们在发展。癌症免疫编辑是对癌症免疫监视假说的完善,并重新将肿瘤与免疫系统之间的复杂相互作用分为三个阶段:消除、平衡和逃逸。
结论:我们对肿瘤免疫原性了解多少,我们如何治疗性地提高肿瘤免疫原性?最近,美国食品和药物管理局 (FDA) 批准了第一个疫苗和第一个免疫调节剂用于治疗前列腺癌(sipuleucel-T)和黑色素瘤(ipilimumab)。未来免疫治疗策略的成功将取决于鉴定出更多可作为最佳肿瘤排斥靶标的免疫原性抗原。治疗的成功将取决于开发最佳抗原传递系统,并阐明调节肿瘤微环境中免疫反应的整个免疫信号通路网络。
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