Construction and characterization of a novel fusion protein consisting of anti-CD3 antibody fused to recombinant interleukin-2.
T cells can be activated in vitro by monoclonal antibodies to CD3 (anti-CD3) to become non-MHC restricted killer cells (CD3-AK). Anti-CD3 activation upregulates the expression of the interleukin (IL)-2 receptors on T cells whose expansion is facilitated by IL-2. The therapeutic effect of in vivo administration of anti-CD3 and IL-2 has been investigated in many types of human cancers. To circumvent the toxicities posed by systemic administration of high-dose IL-2, there is interest in forming a strategy for targeting and concentrating IL-2 at the site where it is needed. This study investigates the feasibility of constructing a novel fusion protein consisting of IL-2 fused to the constant region of anti-CD3 antibody. Our results indicate that the specific IL-2 receptor-binding capability and bioactivity of the IL-2 portion as well as the CD3-binding and biological functions of anti-CD3 portion remain intact in this anti-CD3/IL-2 fusion protein. Thus, cytokines fused to anti-CD3 antibody by genetic engineering is feasible and may provide a new class of immunotherapeutics for cancer.
Lee
Kuan-Der
KD
Department of Hematology and Oncology, Chang Gung Memorial Hospital, Chiayi 613, Taiwan. kdlee@adm.cgmh.org.tw
Chen
Hsin-Wei
HW
Chen
Chih-Cheng
CC
Shih
Yan-Chung
YC
Liu
Hsing-Kun
HK
Cheng
Mei-Lien
ML
D000818:Animals; D000911:Antibodies, Monoclonal / Q000378:metabolism*; D000945:Antigens, Differentiation, T-Lymphocyte / Q000276:immunology*; D017252:CD3 Complex / Q000276:immunology*; D003602:Cytotoxicity, Immunologic; D004591:Electrophoresis, Polyacrylamide Gel; D005260:Female; D005434:Flow Cytometry; D007167:Immunotherapy; D007376:Interleukin-2 / Q000378:metabolism*; D007694:Killer Cells, Natural / Q000276:immunology / Q000378:metabolism; D008213:Lymphocyte Activation; D051379:Mice; D008809:Mice, Inbred C3H; D009374:Neoplasms, Experimental / Q000276:immunology / Q000378:metabolism / Q000628:therapy*; D015375:Receptors, Interleukin-2 / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000627:therapeutic use*; D011994:Recombinant Proteins / Q000378:metabolism; D013601:T-Lymphocytes / Q000276:immunology; D014407:Tumor Cells, Cultured / Q000276:immunology
D000911:Antibodies, Monoclonal; D000945:Antigens, Differentiation, T-Lymphocyte; D017252:CD3 Complex; D007376:Interleukin-2; D015375:Receptors, Interleukin-2; D011993:Recombinant Fusion Proteins; D011994:Recombinant Proteins