许多基础研究表明，自体癌疫苗在黑色素瘤治疗中具有潜力。然而，一些临床试验表明，简单的全肿瘤细胞疫苗只能引起微弱的CD8+ T细胞介导的抗肿瘤反应，这并不足以有效消除肿瘤。因此，需要有效的癌症疫苗传递策略以提高免疫原性。在这里，我们描述了一种新型的混合疫苗“MCL”（Melittin-RADA32-CpG-Lysate），它由蜂毒肽、RADA32、CpG和肿瘤溶解物组成。在这种混合疫苗中，抗肿瘤肽蜂毒肽和自组装融合肽RADA32被组装成水凝胶框架蜂毒肽-RADA32（MR）。然后，整个肿瘤细胞裂解物和免疫佐剂CpG-ODN被装入MR中，形成可注射的细胞毒性水凝胶MCL。 MCL在体外表现出优异的持续药物释放能力，能激活树突状细胞并直接杀死黑色素瘤细胞。在体内，MCL不仅具有直接的抗肿瘤活性，还具有强大的免疫启动效应，包括激活引流淋巴结中的树突状细胞和细胞毒性T淋巴细胞（CTL）在肿瘤微环境中的渗透。此外，MCL能够有效抑制B16-F10肿瘤携带小鼠的黑色素瘤生长，这表明MCL是黑色素瘤治疗的一种潜在癌症疫苗策略。本期刊为©英国皇家化学学会。

Many basic research studies have shown the potential of autologous cancer vaccines in the treatment of melanoma. However, some clinical trials showed that simplex whole tumor cell vaccines can only elicit weak CD8+ T cell-mediated antitumor responses which were not enough for effective tumor elimination. So efficient cancer vaccine delivery strategies with improved immunogenicity are needed. Herein, we described a novel hybrid vaccine "MCL" (Melittin-RADA32-CpG-Lysate) which was composed of melittin, RADA32, CpG and tumor lysate. In this hybrid vaccine, antitumor peptide melittin and self-assembling fusion peptide RADA32 were assembled to form the hydrogel framework melittin-RADA32(MR). Then, whole tumor cell lysate and immune adjuvant CpG-ODN were loaded into MR to develop an injectable and cytotoxic hydrogel MCL. MCL showed excellent ability for sustained drug release, to activate dendritic cells and directly kill melanoma cells in vitro. In vivo, MCL not only exerted direct antitumor activity, but also had robust immune initiation effects including the activation of dendritic cells in draining lymph nodes and the infiltration of cytotoxic T lymphocytes (CTLs) in tumor microenvironment. In addition, MCL can efficiently inhibit melanoma growth in B16-F10 tumor bearing mice, which suggested that MCL is a potential cancer vaccine strategy for melanoma treatment.This journal is © The Royal Society of Chemistry.