In vitro naphthylquinoxaline thymidine conjugate and UVA treated cancer cells are effective therapeutic vaccines for tumors in vivo with CpG as the adjuvant,Journal of Advanced Research

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In vitro naphthylquinoxaline thymidine conjugate and UVA treated cancer cells are effective therapeutic vaccines for tumors in vivo with CpG as the adjuvant
Journal of Advanced Research ( IF 11.4 ) Pub Date : 2021-03-09 , DOI: 10.1016/j.jare.2021.03.003
Rong Yang ₁ , Shanshan Zhou ₁ , Qibing Zhou ₁

Affiliation

Introduction

Cancer cells induced into immunogenic cell death (ICD) in vitro can be directly used as a whole cell vaccine for tumor immunotherapy with many advantages, especially enacting immediate and intense ‘eat me’ signals to engage immune system. Unfortunately, there have been few successes with in vitro ICD cancer cells as a treatment vaccine.

Objective

To demonstrate that cancer cells treated in vitro with a new class of potent ICD inducer, naphthylquinoxaline thymidine conjugate (NAP) followed by UVA irradiation would be able to act as an effective tumor immunotherapy directly.

Methods

The therapeutic potentials of treated cancer cell plus different vaccine adjuvants were assessed by in vivo liver tumor model and in vitro mixed lymphocyte reaction studies. The elicited activated T cells were determined with immunohistochemistry and T cell induced cytotoxicity studies.

Results

Treatment of established H22 tumor with in vitro NAP and UVA treated cancer cell vaccine led to significantly improved survival. Further mixed lymphocyte reaction study implied that adjuvants alum and CpG would improve the therapeutic potential whereas poly IC would not be as effective. Subsequent in vivo validation of alum and CpG adjuvants indicated that only CpG in NAP and UVA treated cell vaccine resulted in markedly enhanced survival (median at 71 days and 50% tumor-free) as compared with PBS group (14.5 days, 0%) and CpG alone (36 days, 0%). It was revealed that the enhanced efficacy by CpG was specific to NAP and UVA treated cells. Moreover, the effective tumor immunotherapy was achieved through the infiltration of active CD4 and CD8 T cells in tumors and acquisition of cancer cell-specific cytotoxic CD8 T cells.

Conclusion

In vitro NAP and UVA treated cancer cells plus CpG adjuvant are effective tumor therapeutic vaccines per se.

中文翻译：

体外萘基喹喔啉胸苷偶联物和 UVA 处理的癌细胞是体内肿瘤的有效治疗疫苗，其中 CpG 作为佐剂

介绍

在体外诱导成免疫原性细胞死亡 (ICD) 的癌细胞可直接用作肿瘤免疫治疗的全细胞疫苗，具有许多优势，特别是可以立即发出强烈的“吃我”信号以参与免疫系统。不幸的是，体外 ICD 癌细胞作为治疗疫苗几乎没有成功。

客观的

为了证明在体外用一类新的强效 ICD 诱导剂处理癌细胞，萘基喹喔啉胸苷偶联物 (NAP) 以及随后的 UVA 照射将能够直接作为一种有效的肿瘤免疫疗法。

方法

通过体内肝肿瘤模型和体外混合淋巴细胞反应研究评估了处理过的癌细胞加不同疫苗佐剂的治疗潜力。用免疫组织化学和 T 细胞诱导的细胞毒性研究确定引发的活化 T 细胞。

结果

用体外 NAP 和 UVA 处理的癌细胞疫苗治疗已建立的 H22 肿瘤可显着提高存活率。进一步的混合淋巴细胞反应研究表明，佐剂明矾和 CpG 将提高治疗潜力，而聚 IC 不会那么有效。随后对明矾和 CpG 佐剂的体内验证表明，与 PBS 组相比（14.5 天，0%）和单独的 CpG（36 天，0%）。结果表明，CpG 增强的功效对 NAP 和 UVA 处理的细胞具有特异性。此外，通过在肿瘤中浸润活性CD4和CD8 T细胞并获得癌细胞特异性细胞毒性CD8 T细胞，实现了有效的肿瘤免疫治疗。