Establishment of a Therapeutic Anti-Pan HLA-Class II Monoclonal Antibody That Directly Induces Lymphoma Cell Death via Large Pore Formation.

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 imm...

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Main Authors: Shuji Matsuoka, Yasuyuki Ishii, Atsuhito Nakao, Masaaki Abe, Naomi Ohtsuji, Shuji Momose, Hui Jin, Hisashi Arase, Koichi Sugimoto, Yusuke Nakauchi, Hiroshi Masutani, Michiyuki Maeda, Hideo Yagita, Norio Komatsu, Okio Hino
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2016-01-01
Series:PLoS ONE
Online Access:http://europepmc.org/articles/PMC4814124?pdf=render
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author Shuji Matsuoka
Yasuyuki Ishii
Atsuhito Nakao
Masaaki Abe
Naomi Ohtsuji
Shuji Momose
Hui Jin
Hisashi Arase
Koichi Sugimoto
Yusuke Nakauchi
Hiroshi Masutani
Michiyuki Maeda
Hideo Yagita
Norio Komatsu
Okio Hino
author_facet Shuji Matsuoka
Yasuyuki Ishii
Atsuhito Nakao
Masaaki Abe
Naomi Ohtsuji
Shuji Momose
Hui Jin
Hisashi Arase
Koichi Sugimoto
Yusuke Nakauchi
Hiroshi Masutani
Michiyuki Maeda
Hideo Yagita
Norio Komatsu
Okio Hino
author_sort Shuji Matsuoka
collection DOAJ
description 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.
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spelling doaj.art-d364300c7b7948fdb551b743738da2ba2022-12-22T01:34:54ZengPublic Library of Science (PLoS)PLoS ONE1932-62032016-01-01113e015049610.1371/journal.pone.0150496Establishment of a Therapeutic Anti-Pan HLA-Class II Monoclonal Antibody That Directly Induces Lymphoma Cell Death via Large Pore Formation.Shuji MatsuokaYasuyuki IshiiAtsuhito NakaoMasaaki AbeNaomi OhtsujiShuji MomoseHui JinHisashi AraseKoichi SugimotoYusuke NakauchiHiroshi MasutaniMichiyuki MaedaHideo YagitaNorio KomatsuOkio HinoTo 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.http://europepmc.org/articles/PMC4814124?pdf=render
spellingShingle Shuji Matsuoka
Yasuyuki Ishii
Atsuhito Nakao
Masaaki Abe
Naomi Ohtsuji
Shuji Momose
Hui Jin
Hisashi Arase
Koichi Sugimoto
Yusuke Nakauchi
Hiroshi Masutani
Michiyuki Maeda
Hideo Yagita
Norio Komatsu
Okio Hino
Establishment of a Therapeutic Anti-Pan HLA-Class II Monoclonal Antibody That Directly Induces Lymphoma Cell Death via Large Pore Formation.
PLoS ONE
title Establishment of a Therapeutic Anti-Pan HLA-Class II Monoclonal Antibody That Directly Induces Lymphoma Cell Death via Large Pore Formation.
title_full Establishment of a Therapeutic Anti-Pan HLA-Class II Monoclonal Antibody That Directly Induces Lymphoma Cell Death via Large Pore Formation.
title_fullStr Establishment of a Therapeutic Anti-Pan HLA-Class II Monoclonal Antibody That Directly Induces Lymphoma Cell Death via Large Pore Formation.
title_full_unstemmed Establishment of a Therapeutic Anti-Pan HLA-Class II Monoclonal Antibody That Directly Induces Lymphoma Cell Death via Large Pore Formation.
title_short Establishment of a Therapeutic Anti-Pan HLA-Class II Monoclonal Antibody That Directly Induces Lymphoma Cell Death via Large Pore Formation.
title_sort establishment of a therapeutic anti pan hla class ii monoclonal antibody that directly induces lymphoma cell death via large pore formation
url http://europepmc.org/articles/PMC4814124?pdf=render
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