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Blood Rev. 2018 Jul;32(4):312-325. doi: 10.1016/j.blre.2018.02.002. Epub 2018 Feb 15.

Anti-cancer vaccine therapy for hematologic malignancies: An evolving era.

Author information

1
Department of Medicine, Beth Israel Deaconess Medical Center, Boston, MA, USA. Electronic address: mnahas1@bidmc.harvard.edu.
2
Department of Medicine, Beth Israel Deaconess Medical Center, Boston, MA, USA.
3
Department of Medicine, Case Western Reserve University, Cleveland, OH, USA.

Abstract

The potential promise of therapeutic vaccination as effective therapy for hematologic malignancies is supported by the observation that allogeneic hematopoietic cell transplantation is curative for a subset of patients due to the graft-versus-tumor effect mediated by alloreactive lymphocytes. Tumor vaccines are being explored as a therapeutic strategy to re-educate host immunity to recognize and target malignant cells through the activation and expansion of effector cell populations. Via several mechanisms, tumor cells induce T cell dysfunction and senescence, amplifying and maintaining tumor cell immunosuppressive effects, resulting in failure of clinical trials of tumor vaccines and adoptive T cell therapies. The fundamental premise of successful vaccine design involves the introduction of tumor-associated antigens in the context of effective antigen presentation so that tolerance can be reversed and a productive response can be generated. With the increasing understanding of the role of both the tumor and tumor microenvironment in fostering immune tolerance, vaccine therapy is being explored in the context of immunomodulatory therapies. The most effective strategy may be to use combination therapies such as anti-cancer vaccines with checkpoint blockade to target critical aspects of this environment in an effort to prevent the re-establishment of tumor tolerance while limiting toxicity associated with autoimmunity.

KEYWORDS:

CAR-T; Checkpoint inhibitors; Dendritic cells; Hematologic malignancy; IMiDs; Immune tolerance; Vaccination

PMID:
29475779
DOI:
10.1016/j.blre.2018.02.002

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