An autologous dendritic cell canine mammary tumor hybrid-cell fusion vaccine.
Summary of "An autologous dendritic cell canine mammary tumor hybrid-cell fusion vaccine."
Mammary cancer is among the most prevalent canine tumors and frequently resulting in death due to metastatic disease that is highly homologous to human breast cancer. Most canine tumors fail to raise effective immune reactions yet, some spontaneous remissions do occur. Hybrid canine dendritic cell-tumor cell fusion vaccines were designed to enhance antigen presentation and tumor immune recognition. Peripheral blood-derived autologous dendritic cell enriched populations were isolated from dogs based on CD11c(+) expression and fused with canine mammary tumor (CMT) cells for vaccination of laboratory Beagles. These hybrid cells were injected into popliteal lymph nodes of normal dogs, guided by ultrasound, and included CpG-oligonucleotide adjuvants. Three rounds of vaccination were delivered. Significant IgG responses were observed in all vaccinated dogs compared to vehicle-injected controls. Canine IgG antibodies recognized shared CMT antigens as was demonstrated by IgG-recognition of three unrelated/independently derived CMT cell lines, and recognition of freshly isolated, unrelated, primary biopsy-derived CMT cells. A bias toward an IgG2 isotype response was observed after two vaccinations in most dogs. Neither significant cytotoxic T cell responses were detected, nor adverse or side-effects due to vaccination or due to the induced immune responses noted. These data provide proof-of-principle for this cancer vaccine strategy and demonstrate the presence of shared CMT antigens that promote immune recognition of mammary cancer.
Affiliation
Department of Pathobiology, Auburn University, Auburn, AL, 36849-5519, USA, birdric@vetmed.auburn.edu.
Journal Details
This article was published in the following journal.
Name: Cancer immunology, immunotherapy : CII
ISSN: 1432-0851
Pages:
Links
- PubMed Source: http://www.ncbi.nlm.nih.gov/pubmed/21069323
- DOI: http://dx.doi.org/10.1007/s00262-010-0921-2
Medical and Biotech [MESH] Definitions
Langerhans Cells
Recirculating, dendritic, antigen-presenting cells containing characteristic racket-shaped granules (Birbeck granules). They are found principally in the stratum spinosum of the EPIDERMIS and are rich in Class II MAJOR HISTOCOMPATIBILITY COMPLEX molecules. Langerhans cells were the first dendritic cell to be described and have been a model of study for other dendritic cells (DCs), especially other migrating DCs such as dermal DCs and INTERSTITIAL DENDRITIC CELLS.
Nuclear Transfer Techniques
Methods of implanting a CELL NUCLEUS from a donor cell into an enucleated acceptor cell. Often the nucleus of a somatic cell is transferred into a recipient OVUM or stem cell (STEM CELLS) with the nucleus removed. This technology may provide means to generate autologous diploid pluripotent cell for therapeutic cloning, and a model for studying NUCLEAR REPROGRAMMING in embryonic stem cells. Nuclear transfer was first accomplished with frog eggs (RANA PIPIENS) and reported in 1952.
Langerhans Cell Sarcoma
Rare malignant neoplasm of dendritic LANGERHANS CELLS exhibiting atypical cytology, frequent mitoses, and aggressive clinical behavior. They can be distinguished from other histiocytic and dendritic proliferations by immunohistochemical and ultrastructure studies. Cytologically benign proliferations of Langerhans cells are called LANGERHANS CELL HISTIOCYTOSIS.
Dendritic Cells, Follicular
Non-hematopoietic cells, with extensive dendritic processes, found in the primary and secondary follicles of lymphoid tissue (the B cell zones). They are different from conventional DENDRITIC CELLS associated with T-CELLS. They are derived from MESENCHYMAL STEM CELLS and are negative for class II MHC antigen and do not process or present antigen like the conventional dendritic cells do. Instead, follicular dendritic cells have FC RECEPTORS and C3B RECEPTORS that hold antigen in the form of ANTIGEN-ANTIBODY COMPLEXES on their surfaces for long periods for recognition by B-CELLS.
Receptor Activator Of Nuclear Factor-kappa B
A tumor necrosis factor receptor family member that is specific for RANK LIGAND and plays a role in bone homeostasis by regulating osteoclastogenesis. It also expressed on DENDRITIC CELLS where is plays a role in regulating dendritic cell survival. Signaling by the activated receptor occurs through its association with TNF RECEPTOR-ASSOCIATED FACTORS.
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