Moores Cancer Center, University of California San Diego, La Jolla, CA, USA.
Biological Sciences Graduate Program, University of California San Diego, La Jolla, CA, USA.
Leukemia. 2022 Apr;36(4):994-1005. doi: 10.1038/s41375-021-01432-w. Epub 2021 Nov 29.
Cancer vaccines are promising treatments to prevent relapse after chemotherapy in acute myeloid leukemia (AML) patients, particularly for those who cannot tolerate intensive consolidation therapies. Here, we report the development of an AML cell membrane-coated nanoparticle (AMCNP) vaccine platform, in which immune-stimulatory adjuvant-loaded nanoparticles are coated with leukemic cell membrane material. This AMCNP vaccination strategy stimulates leukemia-specific immune responses by co-delivering membrane-associated antigens along with adjuvants to antigen-presenting cells. To demonstrate that this AMCNP vaccine enhances leukemia-specific antigen presentation and T cell responses, we modified a murine AML cell line to express membrane-bound chicken ovalbumin as a model antigen. AMCNPs were efficiently acquired by antigen-presenting cells in vitro and in vivo and stimulated antigen cross-presentation. Vaccination with AMCNPs significantly enhanced antigen-specific T cell expansion and effector function compared with control vaccines. Prophylactic vaccination with AMCNPs enhanced cellular immunity and protected against AML challenge. Moreover, in an AML post-remission vaccination model, AMCNP vaccination significantly enhanced survival in comparison to vaccination with whole leukemia cell lysates. Collectively, AMCNPs retained AML-specific antigens, elicited enhanced antigen-specific immune responses, and provided therapeutic benefit against AML challenge.
癌症疫苗是一种很有前途的治疗方法,可以预防急性髓细胞白血病 (AML) 患者化疗后复发,特别是对于那些不能耐受强化巩固治疗的患者。在这里,我们报告了一种 AML 细胞膜包覆的纳米颗粒 (AMCNP) 疫苗平台的开发,其中载有免疫刺激性佐剂的纳米颗粒被白血病细胞膜材料包覆。这种 AMCNP 疫苗接种策略通过将膜相关抗原与佐剂一起递呈给抗原呈递细胞,刺激白血病特异性免疫反应。为了证明这种 AMCNP 疫苗可以增强白血病特异性抗原呈递和 T 细胞反应,我们将一种鼠源 AML 细胞系修饰为表达膜结合鸡卵清蛋白作为模型抗原。AMCNPs 在体外和体内均被抗原呈递细胞有效摄取,并刺激抗原交叉呈递。与对照疫苗相比,AMCNP 疫苗接种显著增强了抗原特异性 T 细胞的扩增和效应功能。预防性 AMCNP 疫苗接种增强了细胞免疫,并防止了 AML 挑战。此外,在 AML 缓解后疫苗接种模型中,与接种整个白血病细胞裂解物相比,AMCNP 疫苗接种显著提高了存活率。总之,AMCNPs 保留了 AML 特异性抗原,引发了增强的抗原特异性免疫反应,并提供了针对 AML 挑战的治疗益处。