Abstract
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.
Highlights
Acute myeloid leukemia (AML) continues to be associated with a poor prognosis, with an overall 5-year survival of ~29% [1]
The lack of well-tolerated and effective consolidation therapy strategies is a major gap in the current AML standard of care, due to the significant morbidity and imperfect prevention of relapse associated with allogeneic hematopoietic stem cell transplantation (HSCT) [5, 6, 47]
We developed an AML cell membrane-coated nanoparticle (AMCNP) vaccination therapy that is personalized, multi-antigenic, and can deliver both membrane-associated leukemic antigens as well as immunostimulatory adjuvants to professional antigen-presenting cells (APCs) in vivo
Summary
Acute myeloid leukemia (AML) continues to be associated with a poor prognosis, with an overall 5-year survival of ~29% [1]. Many patients achieve complete remission after initial induction chemotherapy [2], there remains a high rate of relapse due to the persistence of a small number of therapy-resistant leukemic cells, termed minimal residual disease (MRD) [3, 4]. The current standard treatment strategy to clear MRD is intensive consolidation therapy with allogeneic hematopoietic stem cell transplantation (HSCT) [5]. While the recent approval of various targeted AML therapies has improved survival in certain patient subgroups, relapse after initial therapy remains a large problem [7, 8]. There is a great need for alternative tolerable consolidation therapies that target MRD to delay or prevent relapse
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