Acute myeloid leukemia cell membrane-coated nanoparticles for cancer vaccination immunotherapy

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.

Membrane-wrapped nanoparticles for nucleic acid delivery

“…In the study by Kroll et al, inoculation produced a robust immune response as measured by inflammatory markers and T cell differentiation, which drastically increased cancer cell rejection in vivo. 60 Similar results were obtained in the studies by Johnson et al and Zhang et al, 61,62 affirming the robustness of this approach. Notably, delivering CpG with membranewrapped NPs is advantageous as the targeting properties of the membrane coating can lead to a localized immunostimulatory response.…”

“…Two other groups have proven that CpG 1826-loaded PLGA NPs coated with cell-derived membranes provide robust anticancer effects. 61,62 Johnson et al used C1498 acute myeloid leukemia (AML) cell membranes as an NP coating, 61 while Zhang et al wrapped NPs with hybrid membranes fused from BALB/c-derived bone marrow dendritic cells and ID8 ovarian cancer cells. 62 In a unique approach, Johnson et al administered the AML cell membrane-wrapped NPs (ACMNPs) to mice that were initially challenged with C1498 cells on day 0 and subsequently received chemotherapy on days 1 through 5 to induce remission.…”

“…Impressively, the AMCNPs extended median survival to 4.4 weeks post re-challenge, compared to 2.7 weeks for mice treated with whole cell lysate vaccine. 61 Likewise, the hybrid dendritic cell/cancer cell membrane-wrapped NPs developed by Zhang et al enabled successful treatment of allograft, patient-derived xenograft, and metastatic ovarian cancer tumor models in mice. 62 In the subcutaneous and PDX models the membranewrapped NPs were administered post-tumor challenge, while the NPs were administered prior to tumor challenge in the metastatic model.…”

“…Notably, membrane-wrapped NA carriers can be used not only for gene regulation but also for cancer vaccination by incorporating CpG ODNs as the payload. [60][61][62] These systems use membrane-expressed proteins to support homotypic targeting and increased cell uptake, but also exploit the membrane as an antigen source. The simultaneous delivery of both tumor cell membrane antigens and CpG ODN adjuvants to dendritic cells leads to a potent anti-cancer immune response that is greater than what would be achieved through delivery of antigen or adjuvant alone.…”

Surface Membrane Coating as a Versatile Platform for Modifying Antitumor Nanoparticles

“…40 Simultaneously, homologous targeting adhesion and EPR effect jointly promote the coated nanodrugs to target and effectively aggregate to the tumor site. 41 Therefore, surface coating CCM modification techniques are used to enhance the homogeneous targeting delivery of assembled nanoparticles, 42 LMPN, 43 UCNPs, 41 AuNPs, 44 polymeric nanoparticles, 45 and quantum dots 46 (Figure 2D) into tumors. 47 For example, Li et al developed a biomimetic SPN-based nanocamouflage (AF-SPN) that could specifically target cancer-associated fibroblasts in the tumor microenvironment for enhanced multimodal cancer phototheranostics.…”