title: Establishment of a Therapeutic Anti-Pan HLA-Class II Monoclonal Antibody That Directly Induces Lymphoma Cell Death via Large Pore Formation.
abstract: To develop a new therapeutic monoclonal Antibody (mAb) for Hodgkin lymphoma (HL), we immunized a BALB/c mouse with live HL cell lines, alternating between two HL cell lines. After hybridization, we screened the hybridoma clones by assessing direct cytotoxicity against a HL cell line not used for immunization. We developed this strategy for establishing mAb to reduce the risk of obtaining clonotypic mAb specific for single HL cell line. A newly established mouse anti-human mAb (4713) triggered cytoskeleton-dependent, but complement- and caspase-independent, cell death in HL cell lines, Burkitt lymphoma cell lines, and advanced adult T-cell leukemia cell lines. Intravenous injection of mAb 4713 in tumor-bearing SCID mice improved survival significantly. mAb 4713 was revealed to be a mouse anti-human pan-HLA class II mAb. Treatment with this mAb induced the formation of large pores on the surface of target lymphoma cells within 30 min. This finding suggests that the cell death process induced by this anti-pan HLA-class II mAb may involve the same death signals stimulated by a cytolytic anti-pan MHC class I mAb that also induces large pore formation. This multifaceted study supports the therapeutic potential of mAb 4713 for various forms of lymphoma.
authors.affiliation: Department of Pathology and Oncology, Juntendo University School of Medicine, Tokyo, 113-8421, Japan.
authors.forename: Shuji
authors.initials: S
authors.lastname: Matsuoka
authors.affiliation: RIKEN Research Center for Allergy and Immunology, Yokohama, 204-0022, Japan.
authors.forename: Yasuyuki
authors.initials: Y
authors.lastname: Ishii
authors.affiliation: Department of Immunology, Faculty of Medicine, Yamanashi University, Yamanashi, 409-3898, Japan.
authors.forename: Atsuhito
authors.initials: A
authors.lastname: Nakao
authors.affiliation: Department of Pathology and Oncology, Juntendo University School of Medicine, Tokyo, 113-8421, Japan.
authors.forename: Masaaki
authors.initials: M
authors.lastname: Abe
authors.affiliation: Department of Pathology and Oncology, Juntendo University School of Medicine, Tokyo, 113-8421, Japan.
authors.forename: Naomi
authors.initials: N
authors.lastname: Ohtsuji
authors.affiliation: Department of Pathology and Oncology, Juntendo University School of Medicine, Tokyo, 113-8421, Japan.
authors.forename: Shuji
authors.initials: S
authors.lastname: Momose
authors.affiliation: Department of Immunochemistry, WPI Immunology Frontier Research Center, Osaka University, Osaka, 565-0871, Japan.
authors.forename: Hui
authors.initials: H
authors.lastname: Jin
authors.affiliation: Department of Immunochemistry, WPI Immunology Frontier Research Center, Osaka University, Osaka, 565-0871, Japan.
authors.forename: Hisashi
authors.initials: H
authors.lastname: Arase
authors.affiliation: Department of Hematology and Oncology, JR Tokyo Hospital, Tokyo, 151-8523, Japan.
authors.forename: Koichi
authors.initials: K
authors.lastname: Sugimoto
authors.affiliation: Division of Stem Cell Therapy, Center for Stem Cell Biology and Regenerative Medicine, Institute of Medical Science, The University of Tokyo, Tokyo, 108-8639, Japan.
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Nakauchi
authors.affiliation: Department of Cell Biology, Institute for Virus Research, Kyoto University, Kyoto, 606-8507, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Masutani
authors.affiliation: Department of Cell Biology, Institute for Virus Research, Kyoto University, Kyoto, 606-8507, Japan.
authors.forename: Michiyuki
authors.initials: M
authors.lastname: Maeda
authors.affiliation: Department of Immunology, Juntendo University School of Medicine, Tokyo, 113-8421, Japan.
authors.forename: Hideo
authors.initials: H
authors.lastname: Yagita
authors.affiliation: Division of Hematology, Department of Internal Medicine, Juntendo University School of Medicine, Tokyo, 113-8421, Japan.
authors.forename: Norio
authors.initials: N
authors.lastname: Komatsu
authors.affiliation: Department of Pathology and Oncology, Juntendo University School of Medicine, Tokyo, 113-8421, Japan.
authors.forename: Okio
authors.initials: O
authors.lastname: Hino
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology*; D000970:Antineoplastic Agents / Q000494:pharmacology*; D016923:Cell Death / Q000187:drug effects; D045744:Cell Line, Tumor; D048430:Cell Shape / Q000187:drug effects; D003599:Cytoskeleton / Q000378:metabolism; D057809:HEK293 Cells; D000949:Histocompatibility Antigens Class II / Q000276:immunology; D006801:Humans; D008807:Mice, Inbred BALB C; D008813:Mice, Inbred ICR; D016513:Mice, SCID; D015398:Signal Transduction; D023041:Xenograft Model Antitumor Assays
chemical_list: D000911:Antibodies, Monoclonal; D000970:Antineoplastic Agents; D000949:Histocompatibility Antigens Class II; C000609605:mAB4713 monoconal antibody, mouse