TY - JOUR
T1 - Development of anti-human CADM1 monoclonal antibodies as a potential therapy for adult T-cell leukemia/lymphoma
AU - Chilmi, Syahrul
AU - Nakahata, Shingo
AU - Fauzi, Yanuar Rahmat
AU - Ichikawa, Tomonaga
AU - Tani, Chikako
AU - Suwanruengsri, Mathurot
AU - Yamaguchi, Ryoji
AU - Matsuura, Tadashi
AU - Kurosawa, Gene
AU - Morishita, Kazuhiro
N1 - Funding Information:
The authors are grateful to Dr. Hidekatsu Iha (Oita University, Japan), Dr. Michiyuki Maeda (Kyoto University, Japan), and Dr. Naomichi Arima (Kagoshima University, Japan) for providing cell lines. This work was funded in part by Grant-in-Aid for Scientific Research (B) (25293081 and 17H03581) (KM) from Japan Society for the Promotion of Science (JSPS), by the Takeda Science Foundation (KM) a Research Program on Emerging, and by Re-Emerging Infectious Diseases grant from AMED (18fk0108027h0003) (KM).
PY - 2020/10/1
Y1 - 2020/10/1
N2 - Adult T-cell leukemia/lymphoma (ATLL) is a highly invasive and refractory T-cell malignancy, with poor prognosis. We previously identified that cell adhesion molecule 1 (CADM1) is overexpressed consistently in ATLL cells, and that CADM1 expression increases the adhesion capacity of ATLL cells to endothelial cells and promotes the organ invasion of ATLL cells in a xenograft mouse model. In this study, we first show that newly developed several anti-human CADM1 antibodies, which were complete human IgG antibodies generated by phage display method, specifically recognize CADM1 on ATLL cells. Although most of the CADM1 antibodies did not have a direct cytotoxic effect against CADM1-positive ATLL cells, clone 089–084 exhibited weak but significant antibody-dependent cell-mediated cytotoxic activity. Moreover, clone 103–189 effectively inhibits the interaction between endothelial cells and CADM1-positive ATLL cells. Furthermore, in mice bearing intra-splenic transplantation of EL4 mouse lymphoma cells expressing CADM1, the treatment of 103–189 significantly suppressed the organ invasion of CADM1-positive EL4 cells, resulting in improved survival time of mice. Therefore, since the anti-CADM1 antibody may be useful for the suppression of organ invasion in ATLL patients, combination use of the anti-CADM1 antibody with chemotherapy drugs could be beneficial for the efficient elimination of ATLL cells.
AB - Adult T-cell leukemia/lymphoma (ATLL) is a highly invasive and refractory T-cell malignancy, with poor prognosis. We previously identified that cell adhesion molecule 1 (CADM1) is overexpressed consistently in ATLL cells, and that CADM1 expression increases the adhesion capacity of ATLL cells to endothelial cells and promotes the organ invasion of ATLL cells in a xenograft mouse model. In this study, we first show that newly developed several anti-human CADM1 antibodies, which were complete human IgG antibodies generated by phage display method, specifically recognize CADM1 on ATLL cells. Although most of the CADM1 antibodies did not have a direct cytotoxic effect against CADM1-positive ATLL cells, clone 089–084 exhibited weak but significant antibody-dependent cell-mediated cytotoxic activity. Moreover, clone 103–189 effectively inhibits the interaction between endothelial cells and CADM1-positive ATLL cells. Furthermore, in mice bearing intra-splenic transplantation of EL4 mouse lymphoma cells expressing CADM1, the treatment of 103–189 significantly suppressed the organ invasion of CADM1-positive EL4 cells, resulting in improved survival time of mice. Therefore, since the anti-CADM1 antibody may be useful for the suppression of organ invasion in ATLL patients, combination use of the anti-CADM1 antibody with chemotherapy drugs could be beneficial for the efficient elimination of ATLL cells.
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U2 - 10.1007/s12185-020-02939-1
DO - 10.1007/s12185-020-02939-1
M3 - Article
C2 - 32656636
AN - SCOPUS:85087761266
VL - 112
SP - 496
EP - 503
JO - International Journal of Hematology
JF - International Journal of Hematology
SN - 0925-5710
IS - 4
ER -