癌症疫苗接种后激发有效的抗肿瘤免疫力需要选择性激活不同的效应细胞群和途径。在此，我们报告了一种利用模块化疫苗接种平台技术产生有效 T 细胞反应的治疗方法，该技术能够诱导定向免疫激活，称为类蛋白聚合物 (PLP)。 PLP 表现出增强的蛋白水解抗性、抗原呈递细胞 (APC) 的高摄取以及增强的有效负载特异性 T 细胞反应。改变关键设计参数，即有效负载连接化学、聚合度和侧链组成，以优化疫苗配方。使用细胞内裂解的二硫键与稀释量的寡乙二醇 (OEG) 共聚，将抗原连接到聚合物骨架上，从而产生最高的抗原免疫原性有效负载特异性增强，增强树突状细胞 (DC) 激活和抗原特异性 T细胞反应。使用携带 gp100、E7 或 adpgk 肽的 PLP 进行疫苗接种可显着提高分别接种 B16F10、TC-1 或 MC38 肿瘤的小鼠的存活率，且无需佐剂。当与两种不同的干扰素基因刺激剂 (STING) 激动剂配对时，用携带 gp100 的 PLP 免疫的 B16F10 小鼠表现出抗肿瘤 CD8 T 细胞免疫力增强、肿瘤生长受到抑制以及治疗协同作用。在人乳头瘤病毒相关的 TC-1 模型中，PLP 和 2'3'-cGAMP 联合治疗导致 40% 的小鼠完全消除了植入的肿瘤，同时还表现出针对再次攻击的治疗性保护，这与赋予持久的免疫记忆相一致。最后，PLP 可以以冻干状态长期保存，并且高度可调，强调了该平台用作通用癌症疫苗的独特特性。

Elicitation of effective antitumor immunity following cancer vaccination requires the selective activation of distinct effector cell populations and pathways. Here we report a therapeutic approach for generating potent T cell responses using a modular vaccination platform technology capable of inducing directed immune activation, termed the Protein-like Polymer (PLP). PLPs demonstrate increased proteolytic resistance, high uptake by antigen-presenting cells (APCs), and enhanced payload-specific T cell responses. Key design parameters, namely payload linkage chemistry, degree of polymerization, and side chain composition, were varied to optimize vaccine formulations. Linking antigens to the polymer backbone using an intracellularly cleaved disulfide bond copolymerized with a diluent amount of oligo(ethylene glycol) (OEG) resulted in the highest payload-specific potentiation of antigen immunogenicity, enhancing dendritic cell (DC) activation and antigen-specific T cell responses. Vaccination with PLPs carrying either gp100, E7, or adpgk peptides significantly increased the survival of mice inoculated with B16F10, TC-1, or MC38 tumors, respectively, without the need for adjuvants. B16F10-bearing mice immunized with gp100-carrying PLPs showed increased antitumor CD8+ T cell immunity, suppressed tumor growth, and treatment synergy when paired with two distinct stimulator of interferon gene (STING) agonists. In a human papillomavirus-associated TC-1 model, combination therapy with PLP and 2'3'-cGAMP resulted in 40% of mice completely eliminating implanted tumors while also displaying curative protection from rechallenge, consistent with conferment of lasting immunological memory. Finally, PLPs can be stored long-term in a lyophilized state and are highly tunable, underscoring the unique properties of the platform for use as generalizable cancer vaccines.