Systemic Multifunctional Nanovaccines for Potent Personalized Immunotherapy of Acute Myeloid Leukemia
Peng Zhang1,2, Tanzhen Wang3, Guanhong Cui1,2, Ruonan Ye1,2, Wenjun Wan4, Tianhui Liu3（刘天会）*, Yiran Zheng4（郑毅然）*, Zhiyuan Zhong1,2,4(钟志远)*
1Biomedical Polymers Laboratory, College of Chemistry Chemical Engineering and Materials Science, Soochow University, Suzhou 215123, P. R. China
2State Key Laboratory of Radiation Medicine and Protection, Soochow University, Suzhou 215123, P. R. China
3National Clinical Research Center for Hematologic Diseases, Jiangsu Institute of Hematology, The First Affiliated Hospital of Soochow University, Collaborative Innovation Center of Hematology Soochow University, Suzhou 215000, P. R.
4College of Pharmaceutical Sciences, Suzhou International Joint Laboratory for Diagnosis and Treatment of Brain Diseases Soochow University, Suzhou 215123, P. R. China
Adv. Mater. 2024, 36, 2407189
Abstract: 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.
链接：//onlinelibrary.wiley.com/doi/10.1002/adma.202407189
