title: Challenges in vaccine therapy in hematological malignancies and strategies to overcome them.
abstract: Hematological malignancies (HM) are a promising platform for immunotherapy when considering the marked durable remissions historically achieved through allogeneic stem cell transplantation in select patients. Both non-cell and cell-based vaccine models have been utilized to elicit T cell tumor-specific eradication of malignant cells with resultant striking immunologic effects, but only modest clinical outcomes. In the last decade, the field of oncology has garnered greater insight into the complex mechanisms underpinning immune dysregulation in HM.
  
  
  
  This review addresses the development of vaccine strategies for HM examining the challenges of effectively inducing tumor-specific immunity and overcoming the barriers created by the tumor microenvironment.
  
  
  
  Through a better understanding of the tumor immunosuppressive milieu and immunobiology of HM, rational immunotherapeutic combination therapies can be designed incorporating the potency of vaccine therapy to stimulate native immune responses. In current practice, the use of combinatorial immunotherapies in the treatment of HM is becoming more recognized. This strategy, with vaccines as the backbone, will likely lead to paradigm-changing therapeutic regimens in the decades to come, affording HM patients with durable remissions and improved quality of life.
authors.affiliation: a Section of Hematological Malignancies and Bone Marrow Transplantation , Beth Israel Deaconess Medical Center , Boston , MA , USA.
authors.forename: Myrna R
authors.initials: MR
authors.lastname: Nahas
authors.affiliation: a Section of Hematological Malignancies and Bone Marrow Transplantation , Beth Israel Deaconess Medical Center , Boston , MA , USA.
authors.forename: David
authors.initials: D
authors.lastname: Avigan
mesh_terms: D000818:Animals; D019496:Cancer Vaccines / Q000627:therapeutic use*; D003131:Combined Modality Therapy / Q000379:methods; D019337:Hematologic Neoplasms / Q000276:immunology / Q000628:therapy*; D018380:Hematopoietic Stem Cell Transplantation / Q000379:methods; D006801:Humans; D007167:Immunotherapy / Q000379:methods*; D016233:Immunotherapy, Active / Q000379:methods*; D011788:Quality of Life
chemical_list: D019496:Cancer Vaccines
keywords: CAR T cells; DC fusion vaccines; checkpoint modulation; hematological malignancies; hematological malignancy vaccines; immune dysregulation; immunomodulatory drugs; immunotherapy; tumor microenvironment; tumor-associated antigens