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Generation of Discriminative Human Monoclonal Antibodies from Rare Antigen-specific B Cells Circulating in Blood
Published on: February 6, 2018
Production of antibodies against multipass membrane proteins expressed in human tumor cells using dendritic cell
1Department of Biological Science and Technology, Tokyo University of Science, Noda-shi, Chiba 278-8510, Japan. t-tamura@tg8.so-net.ne.jp
Abstract:
Antibody mediated therapeutic strategies against human malignant tumors have been widely authorized and clinically applied to cancer patients. In order to develop methods to generate antibodies reactive to the extracellular domains of multipass plasma membrane proteins specifically expressed in malignant tumors, we examined the use of dendritic cells (DCs) for immunization. DCs were transduced with genes encoding the human six transmembrane epithelial antigen of prostate 1 (STEAP1), STEAP4, and seven transmembrane prostate specific G-protein coupled receptor (PSGR). Mice were immunized with these DCs and followed by repeated booster immunization with plasmids expressing each protein. The immunized mice produced significant amounts of antibodies against these proteins. Our results suggest that DC immunization is an effective method to produce antibodies reactive to extracellular regions of plasma membrane proteins with multiple-transmembrane domains, and may be useful to develop antibody mediated antitumor therapies.
Insights
Dendritic cell (DC) immunization effectively generated antibodies against tumor-specific membrane proteins. This method shows promise for developing new antibody therapies against malignant tumors.
Area of Science:
- Oncology
- Immunology
- Biotechnology
Background:
- Antibody-mediated therapies are established treatments for human malignant tumors.
- Generating antibodies against extracellular domains of multipass plasma membrane proteins on tumors is challenging.
- Dendritic cells (DCs) are potent antigen-presenting cells that can be used for immunization.
Purpose of the Study:
- To develop an effective method for generating antibodies against extracellular domains of multipass plasma membrane proteins specifically expressed in malignant tumors.
- To evaluate the utility of dendritic cells (DCs) for immunization against tumor-associated antigens.
- To produce antibodies targeting STEAP1, STEAP4, and PSGR, which are expressed in malignant tumors.
Main Methods:
- Dendritic cells (DCs) were transduced with genes encoding STEAP1, STEAP4, and PSGR.
- Mice were immunized with these genetically modified DCs.
- Booster immunizations were performed using plasmids encoding the target proteins.
Main Results:
- The immunization strategy successfully generated significant amounts of antibodies against STEAP1, STEAP4, and PSGR in mice.
- Antibodies produced were reactive to the extracellular regions of these multipass plasma membrane proteins.
- The study demonstrated the feasibility of using DC-based immunization for antibody generation.
Conclusions:
- Dendritic cell (DC) immunization is an effective approach for producing antibodies against extracellular domains of multipass plasma membrane proteins.
- This method holds potential for developing novel antibody-mediated antitumor therapies.
- Targeting tumor-specific membrane proteins via DC-generated antibodies offers a promising avenue for cancer treatment.
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