Hematological malignancies (HM) like acute myeloid leukemia (AML) are often intractable. Cancer vaccines possibly inducing robust and broad anti‐tumor immune responses may be a promising treatment option for HM. Few effective vaccines against blood cancers are, however, developed to date partly owing to insufficient stimulation of dendritic cells (DCs) in the body and lacking appropriate tumor antigens (Ags). Here it is found that systemic multifunctional nanovaccines consisting of nucleotide‐binding oligomerization domain‐containing protein 2 (NOD2) and Toll‐like receptor 9 (TLR9) agonists – muramyl dipeptide (MDP) and CpG, and tumor cell lysate (TCL) as Ags (MCA‐NV) induce potent and broad immunity against AML. MCA‐NV show complementary stimulation of DCs and prime homing to lymphoid organs following systemic administration. Of note, in orthotopic AML mouse models, intravenous infusion of different vaccine formulations elicits substantially higher anti‐AML efficacies than subcutaneous administration. Systemic MCA‐NV cure 78% of AML mice and elicit long‐term immune memory with 100% protection from rechallenging AML cells. Systemic MCA‐NV can also serve as prophylactic vaccines against the same AML. These systemic nanovaccines utilizing patient TCL as Ags and dual adjuvants to elicit strong, durable, and broad immune responses can provide a personalized immunotherapeutic strategy against AML and other HM.

中文翻译：

---

全身多功能纳米疫苗用于急性髓系白血病的有效个体化免疫治疗


血液恶性肿瘤（HM）如急性髓系白血病（AML）通常很棘手。癌症疫苗可能诱导强大而广泛的抗肿瘤免疫反应，可能是 HM 的一种有前途的治疗选择。然而，迄今为止，还没有开发出针对血癌的有效疫苗，部分原因是体内树突状细胞（DC）刺激不足且缺乏适当的肿瘤抗原（Ag）。在此发现，由核苷酸结合寡聚化结构域蛋白2（NOD2）和Toll样受体9（TLR9）激动剂——胞壁酰二肽（MDP）和CpG以及肿瘤细胞裂解物（TCL）作为Ag组成的全身多功能纳米疫苗(MCA-NV) 可诱导针对 AML 的有效且广泛的免疫力。 MCA-NV 显示出对 DC 的补充刺激，并在全身给药后主要归巢至淋巴器官。值得注意的是，在原位 AML 小鼠模型中，静脉输注不同疫苗制剂的抗 AML 功效明显高于皮下注射。全身性 MCA-NV 治愈了 78% 的 AML 小鼠，并引发长期免疫记忆，100% 防止再次攻击 AML 细胞。全身性 MCA-NV 也可以作为针对相同 AML 的预防性疫苗。这些全身性纳米疫苗利用患者 TCL 作为抗原和双重佐剂来引发强烈、持久和广泛的免疫反应，可以提供针对 AML 和其他 HM 的个性化免疫治疗策略。