Department of Oncology, Jiangmen Central Hospital, Affiliated Jiangmen Hospital of Sun Yat-sen University, Jiangmen, China.
Department of Abdominal Oncology, The Cancer Center of the Fifth Affiliated Hospital of Sun Yat-sen University, Zhuhai, China.
Neoplasma. 2023 Dec;70(6):747-760. doi: 10.4149/neo_2023_230125N41. Epub 2023 Nov 28.
Vaccines composed of autophagosomes derived from tumor cells called DRibbles (DRiPs-containing blebs) are involved in the cross-presentation of tumor antigens, thus inducing cross-reactive T-cell responses against the tumor. Compared with traditional tumor lysate vaccines, autophagosome vaccines were found to be better sources of multiple tumor-associated antigens (TAAs) that activate antigen-specific T-cells. However, the involvement of tumor neoantigens in the immune responses of autophagosome vaccines remains unclear. The present study showed that exogenous autophagosome vaccines (DRibbles) combined with immune adjuvants (anti-OX40 antibody and ATP) can effectively activate functional T cells in vitro. Importantly, the combination of exogenous tumor-derived autophagosome vaccines and immune adjuvants was found to induce tumor regression in B16F10 and 4T1 tumor-bearing mice. The combination of autophagosome-enriched DRibbles with anti-OX40 antibody and ATP also exhibited optimal immune stimulation and antitumor efficiency in vivo. The effectiveness of exogenous DRibble vaccines was mainly due to their enhancement of tumor immunogenicity by increasing the presentation and release of tumor neoantigens. These findings suggest that this immunotherapeutic method may be effective in the treatment of cancer.
由源自肿瘤细胞的自噬体组成的疫苗称为 DRibbles（含 DRiPs 的泡状结构），参与肿瘤抗原的交叉呈递，从而诱导针对肿瘤的交叉反应性 T 细胞应答。与传统的肿瘤裂解物疫苗相比，自噬体疫苗被发现是更好的多种肿瘤相关抗原（TAAs）的来源，能够激活抗原特异性 T 细胞。然而，肿瘤新抗原在自噬体疫苗免疫反应中的参与仍不清楚。本研究表明，外源性自噬体疫苗（DRibbles）与免疫佐剂（抗 OX40 抗体和 ATP）联合使用可以有效地在体外激活功能性 T 细胞。重要的是，发现外源性肿瘤来源的自噬体疫苗与免疫佐剂的联合使用可以诱导 B16F10 和 4T1 荷瘤小鼠的肿瘤消退。富含自噬体的 DRibbles 与抗 OX40 抗体和 ATP 的联合使用也在体内表现出最佳的免疫刺激和抗肿瘤效率。外源性 DRibble 疫苗的有效性主要归因于其通过增加肿瘤新抗原的呈递和释放来增强肿瘤免疫原性。这些发现表明，这种免疫治疗方法可能在癌症治疗中有效。
