In this report, we tested; 1) chemokine, which tumor antigen fusion partner and forms of antigen, 2) epitope for enhancing encoded antigen specific T cell immune response, and 3) production of immunotherapeutic auto-antibody. The first, we examined the chemokines, Exodus-1, MCP-1, and RANTES, which ...
In this report, we tested; 1) chemokine, which tumor antigen fusion partner and forms of antigen, 2) epitope for enhancing encoded antigen specific T cell immune response, and 3) production of immunotherapeutic auto-antibody. The first, we examined the chemokines, Exodus-1, MCP-1, and RANTES, which are known to attract both antigen-presenting cells and T cells. We select three different lengths of extramelanosomal region (EMR) of melanoma antigen Pmel17 (gp100) based on CTL epitope and asparagines-linked glycosylation (N-glycosylation) and then fused each of the chemokine genes with selected antigen. The EMR constructs include EMR1 contain only two CTL epitope, EMR2 three CTL epitopes and one glycosylation site, and EMR3 three CTL epitopes and three glycosylation site. We found that only Exodus-1 enhanced the CTL response against EMR, particularly EMR1. Therefore, therapeutic chemokine-TAA-based tumor DNA vaccine should be designed to include the following elements: deglycosylation of TAA gene, conjugation with the proper chemokine to target the expressed antigens to DCs rather than monocytes/macrophages or T cells. A logical goal of immunotherapy by DNA vaccine is to induce selective immune enhancement or suppression against encoded target antigen. To increase immunogenicity, we introduced HA or NP tag, which antibody epitope or CD8+ T cell epitope. Unexpectedly, we show that HA tag elicits enhanced encoded antigen-specific CD8+ T cell response, not NP tag. HA tag-mediated T cell immune response was achieved by suppressed expansion of antigen specific CD4+ T cells or CD4+CD25+ T reg cells and this enhanced immunity. To elicit enhanced immunity by HA-tagged DNA, oligomerized HA tag must ligate to target antigen, Because of only over dimerized HA tag have an intrinsic antigenicity. Increasing immune responses with immunostimulatory monoclonal antibodies (mAbs) directed to immune-receptor molecules is a powerful strategy in cancer therapy. However, side effects such as autoimmunity and systemic inflammation could be induced because of intrinsic immunogenicity of xenogenic mAb when injected that mAbs in mice. Using chemokine-self antigen fusion system, we tested the production of auto-antibody against encoded target antigen and an anti-tumor immunity by induced auto-antibody. We observed m4-1BB specific auto-antibody when Exodus-1-4-1BB plasmid DNA was injected to wild type mice. Anti-4-1BB auto-antibody elicits a synergistic anti-tumor immunity through NK and C8+ T cell dependent manner. But administration of auto-antibody inhibited the cytokine production and proliferation of preactivated CD4+ T cells in vitro assay. Collectively, anti-4-1BB autoAb is different from agonistic anti-4-1BB originated from rat
In this report, we tested; 1) chemokine, which tumor antigen fusion partner and forms of antigen, 2) epitope for enhancing encoded antigen specific T cell immune response, and 3) production of immunotherapeutic auto-antibody. The first, we examined the chemokines, Exodus-1, MCP-1, and RANTES, which are known to attract both antigen-presenting cells and T cells. We select three different lengths of extramelanosomal region (EMR) of melanoma antigen Pmel17 (gp100) based on CTL epitope and asparagines-linked glycosylation (N-glycosylation) and then fused each of the chemokine genes with selected antigen. The EMR constructs include EMR1 contain only two CTL epitope, EMR2 three CTL epitopes and one glycosylation site, and EMR3 three CTL epitopes and three glycosylation site. We found that only Exodus-1 enhanced the CTL response against EMR, particularly EMR1. Therefore, therapeutic chemokine-TAA-based tumor DNA vaccine should be designed to include the following elements: deglycosylation of TAA gene, conjugation with the proper chemokine to target the expressed antigens to DCs rather than monocytes/macrophages or T cells. A logical goal of immunotherapy by DNA vaccine is to induce selective immune enhancement or suppression against encoded target antigen. To increase immunogenicity, we introduced HA or NP tag, which antibody epitope or CD8+ T cell epitope. Unexpectedly, we show that HA tag elicits enhanced encoded antigen-specific CD8+ T cell response, not NP tag. HA tag-mediated T cell immune response was achieved by suppressed expansion of antigen specific CD4+ T cells or CD4+CD25+ T reg cells and this enhanced immunity. To elicit enhanced immunity by HA-tagged DNA, oligomerized HA tag must ligate to target antigen, Because of only over dimerized HA tag have an intrinsic antigenicity. Increasing immune responses with immunostimulatory monoclonal antibodies (mAbs) directed to immune-receptor molecules is a powerful strategy in cancer therapy. However, side effects such as autoimmunity and systemic inflammation could be induced because of intrinsic immunogenicity of xenogenic mAb when injected that mAbs in mice. Using chemokine-self antigen fusion system, we tested the production of auto-antibody against encoded target antigen and an anti-tumor immunity by induced auto-antibody. We observed m4-1BB specific auto-antibody when Exodus-1-4-1BB plasmid DNA was injected to wild type mice. Anti-4-1BB auto-antibody elicits a synergistic anti-tumor immunity through NK and C8+ T cell dependent manner. But administration of auto-antibody inhibited the cytokine production and proliferation of preactivated CD4+ T cells in vitro assay. Collectively, anti-4-1BB autoAb is different from agonistic anti-4-1BB originated from rat
※ AI-Helper는 부적절한 답변을 할 수 있습니다.