PDF(Pubmed)
Abstract：
Cancer vaccines are gaining ground as immunotherapy options. We have previously demonstrated in cutaneous melanoma (CM) patients that adjuvant treatment with VACCIMEL, a mixture of four irradiated CM cell lines co-adjuvanted with BCG and GM-CSF, increases the cellular immune response to melanocyte differentiation antigens, cancer-testis antigens and neoantigens, with respect to basal levels. On the other hand, it is also known that treatment with anti-PD-1 monoclonal antibodies (MAbs), acting on pre-existing tumor-reactive lymphocytes, induces clinical responses in CM patients, albeit in a fraction of treated patients. A combination of both treatments would appear therefore desirable. In this paper, we describe CM patients who, having progressed even years after vaccination, were treated with anti-PD-1 MAbs. In 5/5 of such progressor patients, complete responses were obtained which lasted between 3 and 65+ months. Three of the patients remain disease-free and two recurred. One of the patients passed away after a recurrence of brain metastases. We suggest that clonally expanded reactive lymphocytes induced by VACCIMEL partially remain as memory cells, which may be recalled after tumor recurrence and may foster ulterior activity of anti-PD-1 MAbs.
摘要：
癌症疫苗作为免疫疗法的选择正在取得进展。我们以前已经在皮肤黑色素瘤（CM）患者中证明了用VACCIMEL辅助治疗，四种照射的CM细胞系与BCG和GM-CSF共佐剂的混合物，增加对黑素细胞分化抗原的细胞免疫反应，癌症-睾丸抗原和新抗原，关于基础水平。另一方面,还已知用抗PD-1单克隆抗体（MAb）治疗，作用于预先存在的肿瘤反应性淋巴细胞，在CM患者中诱导临床反应，尽管在一小部分接受治疗的患者中。因此,两种治疗的组合似乎是理想的。在本文中,我们描述了CM患者，即使在接种疫苗后几年也取得了进展，用抗PD-1单克隆抗体治疗。在5/5的此类进展患者中，获得了持续3至65个月的完整响应。其中三名患者保持无病状态，两名复发。其中一名患者在脑转移复发后去世。我们建议VACCIMEL诱导的克隆扩增的反应性淋巴细胞部分保留为记忆细胞，这可能会在肿瘤复发后被召回，并可能促进抗PD-1单克隆抗体的先兆活性。
