Targeted cytotoxic effect of anti-JL1 immunotoxin against a human leukemic cell line and its clinical implications.
We have previously reported the identification of a unique thymocyte-specific surface molecule, JL1, which was detected using the monoclonal antibody (mAb), anti-JL1. Interestingly, JL1 was shown to be expressed in most leukemias, irrespective of their immunophenotype, and subpopulations of normal bone marrow (BM) mononuclear cells (MNCs). Here we investigated the potential usefulness of the anti-JL1 mAb as a therapeutic tool for leukemia. We demonstrated that the proliferation of cultured human leukemia cells was dramatically inhibited in vitro by anti-JL1 mAb conjugated with the polypeptide toxin, gelonin, but not by gelonin alone. We then systematically investigated the reactivity of the anti-JL1 mAb against normal human tissues to evaluate possible side effects along with various hematopoietic and nonhematopoietic tumor cell lines. All of 33 types of normal tissues except thymus and subpopulation of BM MNCs were clearly devoid of JL1 expression. Among tumor cell lines, all the nonhematopoietic cell lines tested were negative for JL1 expression, while some hematopoietic cell lines contained JL1 antigen. Collectively, the results showed the cytotoxic effects of anti-JL1-based immunotoxin against JL1-positive leukemic cells, sparing most normal tissues other than thymocytes and some BM MNCs. Therefore, we strongly suggest that gelonin-conjugated anti-JL1 mAb immunotoxin could be developed as a potential immunotherapeutic agent in the treatment of various types of JL1-positive acute leukemias.
Shin
Young Kee
YK
Department of Pathology, Seoul National University College of Medicine, 28 Yongon-dong, Chongno-gu, 110-799, Seoul, Korea.
Choi
Yoon La
YL
Choi
Eun Young
EY
Kim
Min Kyung
MK
Kook
Myeong-Cherl
MC
Chung
Junho
J
Choi
Yang-Kyu
YK
Kim
Heung Sik
HS
Song
Hyung Geun
HG
Park
Seong Hoe
SH
D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D000945:Antigens, Differentiation, T-Lymphocyte / Q000276:immunology*; D000951:Antigens, Neoplasm / Q000032:analysis; D000972:Antineoplastic Agents, Phytogenic / Q000627:therapeutic use*; D002470:Cell Survival; D003602:Cytotoxicity, Immunologic; D006801:Humans; D007124:Immunoenzyme Techniques; D000922:Immunotoxins; D007938:Leukemia / Q000188:drug therapy*; D051379:Mice; D010940:Plant Proteins / Q000627:therapeutic use*; D054789:Ribosome Inactivating Proteins, Type 1; D014407:Tumor Cells, Cultured
D000911:Antibodies, Monoclonal; D000945:Antigens, Differentiation, T-Lymphocyte; D000951:Antigens, Neoplasm; D000972:Antineoplastic Agents, Phytogenic; D000922:Immunotoxins; C114952:JL1 antigen; D010940:Plant Proteins; D054789:Ribosome Inactivating Proteins, Type 1; C025674:GEL protein, Gelonium multiflorum