Re-targeting of cytotoxic T lymphocytes and/or natural killer cells to CEA-expressing tumor cells with anti-CEA antibody activity.
Cellular immunity, in which cytotoxic T lymphocytes (CTLs) and natural killer (NK) cells are main effector cells, plays an important role in the antitumor defense mechanism. T cell immunotherapy is based on the assumption that tumor antigen (TA) peptides are correctly presented by HLA class I molecules on target tumor cells, while NK cell immunotherapy is based on the hypothesis that cell surface TAs or ligands for NK receptors are widely expressed in tumor cells. However, human tumor cells are well known to often lose HLA class 1 molecules, and target cell ligands for NK receptors are not always expressed in human tumor cells. This altered HLA class 1 expression and non-ubiquitous distribution of NK receptor ligands constitute the major tumor escape mechanism facing tumor-specific CTL and/or NK cell-mediated responses. These facts also indicate that it is not easy to eliminate the target tumors only by activating tumor-specific CTLs or NK cells. On the other hand, although the protective role of humoral immunity in cancer seems not to be imperative, it is easily confirmed by immunostaining whether or not antibody-recognized TAs such as carcinoembryonic antigen (CEA) exist on the cell surface of target tumor cells. Therefore, endowing CTLs or NK cells with antigen-binding specificity of anti-TA antibody is promising for re-targeting the activities of these effector cells to tumor cells in an HLA-independent manner. This mini-review provides a brief overview of the following four technologies for re-targeting CTLs or NK cells to CEA-expressing tumor cells with anti-CEA antibody activity: i) bispecific antibody technology, ii) antibody-cytokine fusion protein technology, iii) chimeric immune receptor technology, and iv) antibody-HLA/peptide complex technology.
Kuroki
Masahide
M
Department of Biochemistry, Fukuoka University School of Medicine, Fukuoka, Japan. kurokima@fukuoka-u.ac.jp
Hachimine
Ken
K
Huang
Jian
J
Shibaguchi
Hirotomo
H
Kinugasa
Tetsushi
T
Maekawa
Shin-Ichi
S
Kuroki
Motomu
M
D000818:Animals; D000906:Antibodies / Q000276:immunology* / Q000627:therapeutic use; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000627:therapeutic use; D002272:Carcinoembryonic Antigen / Q000096:biosynthesis / Q000276:immunology*; D006680:HLA Antigens / Q000276:immunology; D006801:Humans; D018796:Immunoconjugates / Q000276:immunology / Q000627:therapeutic use; D007128:Immunoglobulin Fragments / Q000276:immunology / Q000627:therapeutic use; D007694:Killer Cells, Natural / Q000276:immunology*; D009369:Neoplasms / Q000276:immunology* / Q000628:therapy*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*
D000906:Antibodies; D000911:Antibodies, Monoclonal; D002272:Carcinoembryonic Antigen; D006680:HLA Antigens; D018796:Immunoconjugates; D007128:Immunoglobulin Fragments