A cell membrane modification technique using domain 4 of intermedilysin for immunotherapy against cancer.
Rapid cell membrane modification techniques are currently being sought in order to develop gene therapy and cellular immunotherapy modalities against cancer and other diseases. We developed a novel technique using the non-toxic portion of intermedilysin, a streptolysin O family cytolysin with a high affinity for human cell membranes, as a cell membrane adaptor module. Domain 4 recombinants of intermedilysin with linker sites at the N-terminus were designed. These modules are able to bind tightly to human cells after simple incubation and have no harmful effects. The modules were conjugated with the partially reduced or unreduced F(ab')2 of an anti-carcinoembryonic antigen monoclonal antibody. Erythrocytes bound to these conjugates were shown to specifically target a carcinoembryonic antigen-positive cell line, TT, in vitro. This is a promising technique for the development of convenient and effective anticancer treatment methods.
Nagamune
Hideaki
H
Department of Biological Science and Technology, Faculty of Engineering, University of Tokushima, Minami-josanjima-cho, Tokushima, Japan. nagamune@bio.tokushima-u.ac.jp
Ohkura
Kazuto
K
Umezu
Kazunori
K
Shouji
Hidekatsu
H
Kourai
Hiroki
H
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000378:metabolism; D001426:Bacterial Proteins; D001430:Bacteriocins; D002272:Carcinoembryonic Antigen / Q000276:immunology; D018276:Carcinoma, Medullary / Q000276:immunology / Q000378:metabolism / Q000628:therapy; D045744:Cell Line, Tumor; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D003603:Cytotoxins / Q000138:chemical synthesis / Q000378:metabolism* / Q000627:therapeutic use*; D004910:Erythrocyte Membrane / Q000187:drug effects / Q000378:metabolism; D004912:Erythrocytes / Q000276:immunology / Q000378:metabolism; D006801:Humans; D018796:Immunoconjugates / Q000737:chemistry / Q000276:immunology / Q000378:metabolism; D007128:Immunoglobulin Fragments / Q000276:immunology / Q000378:metabolism; D007167:Immunotherapy / Q000379:methods*; D017434:Protein Structure, Tertiary; D011817:Rabbits; D011994:Recombinant Proteins / Q000737:chemistry / Q000378:metabolism; D013964:Thyroid Neoplasms / Q000276:immunology / Q000378:metabolism / Q000628:therapy
D000911:Antibodies, Monoclonal; D001426:Bacterial Proteins; D001430:Bacteriocins; D002272:Carcinoembryonic Antigen; D003603:Cytotoxins; D018796:Immunoconjugates; D007128:Immunoglobulin Fragments; D011994:Recombinant Proteins; C403910:intermedilysin protein, Streptococcus intermedius