• Biomolecules & Therapeutics
• /
• 제3권4호
• /
• pp.273-278
• /
• 1995

The effect of methamphetamine on the pulmonary metastasis was investigated in C57BL/6 mice injected with Bl6 melanoma cells. Bl6 melanoma cells (2$\times$10$^{5}$ cells) were injected intravenously into 5~7 weeks old C57BL/6 mice. Mice were then treated intraperitoneally with methamphetamine either acutely (two times with one week interval) or subchronically (daily for 14 days). Degree of pulmonary metastasis was investigated and specific immunologic parameters such as natural killer cell cytotoxicity(NKCC), antibody-dependent cellular cytotoxicity(ADCC) and blastogenic responses of splenocytes were examined. Mice which had been subchronically treated with methamphetamine showed significant decreases in the number of pulmonary metastasis of Bl6 melanoma cells, NKCC and ADCC without a significant change in blastogenic responses. In the acutely-treated group, slight trends of decrease in the numbers of pulmonary metastasis, NKCC and ADCC were observed without statistical significances whereas there was a significant increase in blastogenic responses. The mechanism underlying the decrease in the degree of metastasis despite diminished NKCC and ADCC after methamphetamine treatment and the relationship between the degree of pulmonary metastasis and duration of methamphetamine treatment remain to be investigated.

• Biomolecules & Therapeutics
• /
• 제29권2호
• /
• pp.166-174
• /
• 2021

Multiple myeloma is a malignant cancer of plasma cells. Despite recent progress with immunomodulatory drugs and proteasome inhibitors, it remains an incurable disease that requires other strategies to overcome its recurrence and non-response. Based on the high expression levels of programmed death-ligand 1 (PD-L1) in human multiple myeloma isolated from bone marrow and the murine myeloma cell lines, NS-1 and MOPC-315, we propose PD-L1 molecule as a target of anti-multiple myeloma therapy. We developed a novel anti-PD-L1 antibody containing a murine immunoglobulin G subclass 2a (IgG2a) fragment crystallizable (Fc) domain that can induce antibody-dependent cellular cytotoxicity. The newly developed anti-PD-L1 antibody showed significant antitumor effects against multiple myeloma in mice subcutaneously, intraperitoneally, or intravenously inoculated with NS-1 and MOPC-315 cells. The anti-PD-L1 effects on multiple myeloma may be related to a decrease in the immunosuppressive myeloid-derived suppressor cells (MDSCs), but there were no changes in the splenic MDSCs after combined treatment with lenalidomide and the anti-PD-L1 antibody. Interestingly, the newly developed anti-PD-L1 antibody can induce antibody-dependent cellular cytotoxicity in the myeloma cells, which differs from the existing anti-PD-L1 antibodies. Collectively, we have developed a new anti-PD-L1 antibody that binds to mouse and human PD-L1 and demonstrated the antitumor effects of the antibody in several syngeneic murine myeloma models. Thus, PD-L1 is a promising target to treat multiple myeloma, and the novel anti-PD-L1 antibody may be an effective anti-myeloma drug via antibody-dependent cellular cytotoxicity effects.

• Asian Pacific Journal of Cancer Prevention
• /
• 제13권8호
• /
• pp.4037-4043
• /
• 2012

Despite progress in elucidating mechanisms associated with colorectal cancer and improvement of treatment methods, it remains a frequent cause of death worldwide. New and more effective therapies are therefore urgently needed. Recent studies have shown that immunogenicity of whole ovarian tumor cells and subsequent T cell response were potentiated by oxidation modification with hypochlorous acid (HOCl) in vitro and ex vivo. These results prompted us to investigate the protective antitumor response with an HOCl treated CT26 colorectal cancer cell vaccine in an in vivo mouse model. Administration of HOCl modified vaccine triggered robust antitumor immunity to autologous tumor cells in mice and prolonged survival period significantly. In addition, increased necrosis and apoptosis were found in tumor tissue from the oxidation group. Interestingly, ELISPOT assays showed that specific T cell responses were not elicited in response to the immunizing cellular antigen, in contrast to raising sera antibody titer and antibody binding activity shown by ELISA assay and flow cytometry. Further evaluation of the mechanisms underlying HOCl modified vaccine mediated humoral immunity highlighted the role of antibody-dependent cell-mediated cytotoxicity. These results combined with previous studies suggest that HOCl oxidation modified whole cell vaccine has wide applicability as a cancer vaccine because it can target both T cell- and B cell-specific responses. It may thus represent a promising approach for the immunotherapy of colorectal cancer.