Clinical trials of dendritic cell-based cancer vaccines in hematologic malignancies

Hum Vaccin Immunother. 2014;10(11):3125-31. doi: 10.4161/21645515.2014.982993.

Abstract

The potential for the immune system to target hematological malignancies is demonstrated in the allogeneic transplant setting, where durable responses can be achieved. However, allogeneic transplantation is associated with significant morbidity and mortality related to graft versus host disease. Cancer immunotherapy has the capacity to direct a specific cytotoxic immune response against cancer cells, particularly residual cancer cells, in order to reduce the likelihood of disease relapse in a more targeted and tolerated manner. Ex vivo dendritic cells can be primed in various ways to present tumor associated antigen to the immune system, in the context of co-stimulatory molecules, eliciting a tumor specific cytotoxic response in patients. Several approaches to prime dendritic cells and overcome the immunosuppressive microenvironment have been evaluated in pre-clinical and early clinical trials with promising results. In this review, we summarize the clinical data evaluating dendritic cell based vaccines for the treatment of hematological malignancies.

Keywords: AML, Acute Myeloid Leukemia; ASCT, Autologous Stem Cell Transplant; Apo-DC, Apoptotic body loaded- dendritic cells; CML, Chronic Myeloid Leukemia; CR, Complete response; CTLA-4, Cytotoxic T-Lymphocyte Antigen 4; DC/AML, Dendritic cell Acute Myeloid Leukemia fusion vaccine; DC/MM, Dendritic cell Multiple Myeloma fusion vaccine; DNA Deoxyribonucleic acid; FLT-ITD, Fms-like Tyrosine Kinase with Internal Tandem Duplication; GMCSF, Granulocyte macrophage colony-stimulating factor; GVHD, Graft vs Host Disease; HLA-A*2402, Human Leukocyte antigen A*2402; IFN, Interferon; IFNg, Interferon gamma; IL, Interleukin; Id, Idiotype; KLH, Keyhole limpet hemocyanin; MDS, Myelodysplastic syndrome; MHC, Major histocompatibility complex; OS, Overall Survival; PD-1, Programmed death 1; PD-L1, Programmed death-ligand 1; PR, Partial response; PRR, Pathogen recognition receptor; RNA, Ribonucleic acid; SCT, Stem cell transplant; TGFB, Transforming growth factor β; TNFα, Tumor necrosis factor α; VEGF, Vascular endothelial growth factor; VGPR, Very good partial response; WT-1, Wilm's tumor suppressor gene 1; cancer; dendritic cell; immunotherapy; leukemia; mRNA, mRNA; myeloma; pDCs, Plasmacytoid Dendritic cell; trial; vaccine.

Publication types

  • Review

MeSH terms

  • Antigens, Neoplasm / immunology
  • Cancer Vaccines / immunology
  • Cancer Vaccines / therapeutic use*
  • Clinical Trials as Topic
  • Dendritic Cells / immunology
  • Dendritic Cells / transplantation*
  • Graft vs Host Disease / immunology
  • Hematologic Neoplasms / immunology
  • Hematologic Neoplasms / therapy*
  • Humans
  • Immunotherapy, Adoptive / methods*
  • Transplantation, Homologous
  • Vaccination

Substances

  • Antigens, Neoplasm
  • Cancer Vaccines