After decades of cancer vaccine efforts, there is an imperious necessity for novel ideas that may result in better tumor control in patients. We have proposed the use of a novel Variable Epitope Library (VEL) vaccine strategy, which incorporates an unprecedented number of mutated epitopes to target antigenic variability and break tolerance against tumor-associated antigens. Here, we used an oncofetal antigen/immature laminin receptor protein-derived sequence to generate 9-mer and 43-mer VEL immunogens. 4T1 tumor-bearing mice developed epitope-specific CD8+IFN-γ+ and CD4+IFN-γ+ T cell responses after treatment. Tumor and lung analysis demonstrated that VELs could increase the number of tumor-infiltrating lymphocytes with diverse effector functions while reducing the number of immunosuppressive myeloid-derived suppressor and regulatory T cells. Most importantly, VEL immunogens inhibited tumor growth and metastasis after a single dose. The results presented here are consistent with our previous studies and provide evidence for VEL immunogens’ feasibility as promising cancer immunotherapy.

经过几十年的癌症疫苗努力，迫切需要新的想法来更好地控制患者的肿瘤。我们提议使用一种新的可变表位库 (VEL) 疫苗策略，该策略结合了前所未有的突变表位数量，以针对抗原变异性和对肿瘤相关抗原的破坏耐受性。在这里，我们使用癌胎抗原/未成熟层粘连蛋白受体蛋白衍生序列来生成 9 聚体和 43 聚体 VEL 免疫原。4T1 荷瘤小鼠在治疗后产生表位特异性 CD8+IFN-γ+ 和 CD4+IFN-γ+ T 细胞反应。肿瘤和肺分析表明，VEL 可以增加具有多种效应功能的肿瘤浸润淋巴细胞的数量，同时减少免疫抑制性骨髓源性抑制和调节性 T 细胞的数量。最重要的是，VEL 免疫原在单次给药后抑制了肿瘤的生长和转移。这里呈现的结果与我们之前的研究一致，并为 VEL 免疫原作为有前途的癌症免疫疗法的可行性提供了证据。