Background:Personalized cancer vaccines (PCVs) are a promising form of cancer immunotherapy, capable of eliciting robust neoantigen-specific immune responses. However, cancer neoantigens are variable in terms of immunogenicity, and PCVs may be less effective when targeting weak neoantigens. Strong and durable immune responses are also likely to be critical for vaccine efficacy. Interleukin-7 (IL-7) is a common gamma-chain cytokine known to support T cell development and survival, and a long-acting form of recombinant human IL-7 fused with hybrid Fc (rhIL-7-hyFc) has shown potential to enhance immune responses in early-stage clinical trials.Methods:In this study, we evaluated the ability of rhIL-7-hyFc to serve as a molecular adjuvant to a DNA PCV in the E0771 murine breast cancer model.Results: We found that the combination of rhIL-7-hyFc and DNA PCV treatment prolonged neoantigen-specific CD8+ T cell responses, improved functional memory as measured based on in vivo cytotoxicity, and increased the number of neoantigen-specific tumor-infiltrating lymphocytes (TILs), resulting in improved prophylactic tumor protection and durable memory responses.Conclusions:Our findings support the potential of rhIL-7-hyFc to enhance the efficacy of PCVs and suggest clinical utility for adjuvant rhIL-7-hyFc in cancer immunotherapy.
背景：个性化癌症疫苗（PCVs）是一种前景广阔的癌症免疫疗法，能够引发强烈的新抗原特异性免疫反应。然而，癌症新抗原的免疫原性存在差异，针对弱新抗原时PCVs可能效果不佳。强烈且持久的免疫反应对疫苗效力也至关重要。白细胞介素-7（IL-7）是一种已知能支持T细胞发育和存活的常见γ链细胞因子，而长效型重组人IL-7与杂交Fc融合蛋白（rhIL-7-hyFc）在早期临床试验中已显示出增强免疫反应的潜力。 方法：本研究在E0771小鼠乳腺癌模型中评估了rhIL-7-hyFc作为DNA PCV分子佐剂的能力。 结果：我们发现rhIL-7-hyFc与DNA PCV联合治疗能延长新抗原特异性CD8+ T细胞反应，通过体内细胞毒性检测证实其改善了功能性记忆，并增加了新抗原特异性肿瘤浸润淋巴细胞（TILs）的数量，从而增强了预防性肿瘤保护效果并诱导了持久的记忆反应。 结论：我们的研究结果支持rhIL-7-hyFc具有增强PCVs疗效的潜力，表明佐剂rhIL-7-hyFc在癌症免疫治疗中具有临床应用价值。
肿瘤(癌症)患者之家