Department of Biomedical and Molecular Sciences, Queen's University, Kingston, ON, Canada.
Department of Pathology and Molecular Medicine, Queen's University, Kingston, ON, Canada.
Front Immunol. 2022 Apr 21;13:884827. doi: 10.3389/fimmu.2022.884827. eCollection 2022.
The protocol used to induce cell death for generating vaccines from whole tumor cells is a critical consideration that impacts vaccine efficacy. Here we compared how different protocols used to induce cell death impacted protection provided by a prophylactic whole tumor cell vaccine in a mouse melanoma model. We found that melanoma cells exposed to γ-irradiation or lysis combined with UV-irradiation (LyUV) provided better protection against tumor challenge than lysis only or cells exposed to UV-irradiation. Furthermore, we found that the immunoregulatory cytokine, IL-27 enhanced protection against tumor growth in a dose-dependent manner when combined with either LyUV or γ-irradiated whole tumor cell vaccine preparations. Taken together, this data supports the use of LyUV as a potential protocol for developing whole tumor cell prophylactic cancer vaccines. We also showed that IL-27 can be used at low doses as a potent adjuvant in combination with LyUV or γ-irradiation treated cancer cells to improve the protection provided by a prophylactic cancer vaccine in a mouse melanoma model.
从整个肿瘤细胞生成疫苗时使用的诱导细胞死亡的方案是影响疫苗效果的一个关键考虑因素。在这里，我们比较了不同的诱导细胞死亡方案如何影响小鼠黑色素瘤模型中预防性全肿瘤细胞疫苗提供的保护。我们发现，与仅裂解或暴露于紫外线照射的细胞相比，γ-辐照或裂解联合紫外线照射（LyUV）处理的黑色素瘤细胞能更好地预防肿瘤攻击。此外，我们发现，免疫调节细胞因子 IL-27 与 LyUV 或γ-辐照的全肿瘤细胞疫苗制剂联合使用时，以剂量依赖的方式增强了对肿瘤生长的保护作用。总的来说，这些数据支持将 LyUV 作为开发全肿瘤细胞预防性癌症疫苗的潜在方案。我们还表明，IL-27 可以作为一种有效的佐剂，以低剂量与 LyUV 或γ-辐照处理的癌细胞联合使用，以提高小鼠黑色素瘤模型中预防性癌症疫苗提供的保护。
