Back to Search
Start Over
DCOne as an Allogeneic Cell-based Vaccine for Multiple Myeloma.
- Source :
-
Journal of immunotherapy (Hagerstown, Md. : 1997) [J Immunother] 2017 Nov/Dec; Vol. 40 (9), pp. 315-322. - Publication Year :
- 2017
-
Abstract
- Multiple myeloma (MM) is characterized by progressive immune dysregulation, loss of myeloma-specific immunity, and an immunosuppressive milieu that fosters disease growth and immune escape. Accordingly, cancer vaccines that reverse tumor-associated immune suppression represent a promising therapeutic avenue of investigation. We examined the potential of an allogeneic cellular vaccine to generate immune responses against MM tumor cells. The DCOne vaccine is comprised of a human myeloid leukemia cell line differentiated into a fully functional dendritic cell, expressing a range of tumor-associated antigens that are also known targets in MM. We found that the myeloma-specific antigens expressed by the DCOne vaccine can traffic via extracellular vesicles to surrounding antigen-presenting cells, thus stimulating autologous T-cell responses. Indeed, coculture of peripheral blood mononuclear cells from patients with MM with the DCOne vaccine resulted in the expansion of activated CD8 T cells expressing interferon-γ and perforin, with no significant change in the percentage of CD4 T cells producing interleukin-10. Further, coculture of patient's tumor cells with peripheral blood mononuclear cells and DCOne induced cytotoxic T-lymphocyte-mediated killing of autologous MM cells. These findings demonstrate that the allogeneic DCOne vaccine can induce T-cell activation and myeloma-specific immunity via cross presentation of antigens by native antigen-presenting cells.
- Subjects :
- Cancer Vaccines
Cell Differentiation
Cell Line, Tumor
Coculture Techniques
Cross-Priming
Cytotoxicity, Immunologic
Dendritic Cells transplantation
Humans
Interferon-gamma metabolism
Isoantigens immunology
Lymphocyte Activation
Multiple Myeloma immunology
Perforin metabolism
Tumor Microenvironment
Antigens, Neoplasm immunology
CD8-Positive T-Lymphocytes immunology
Dendritic Cells immunology
Extracellular Vesicles immunology
Immunotherapy, Adoptive methods
Multiple Myeloma therapy
Subjects
Details
- Language :
- English
- ISSN :
- 1537-4513
- Volume :
- 40
- Issue :
- 9
- Database :
- MEDLINE
- Journal :
- Journal of immunotherapy (Hagerstown, Md. : 1997)
- Publication Type :
- Academic Journal
- Accession number :
- 28961609
- Full Text :
- https://doi.org/10.1097/CJI.0000000000000185