Specific activation of resting T cells against CA19-9+ tumor cells by an anti-CD3/CA19-9 bispecific antibody in combination with a costimulatory anti-CD28 antibody.
Specific activation of resting lymphocytes for tumor targeting can be achieved by bispecific monoclonal antibodies (bi-mAb) with specificity for tumor antigens and T-cell-activating antigens, respectively, in combination with a costimulatory anti-CD28 antibody. We describe the generation and function of a bi-mAb with specificity for CD3 and for the tumor antigen CA19-9. The bi-mAb OKT3/NSI19-9 was generated by somatic fusion of two hybridoma lines secreting antibodies against CA19-9 and CD3, respectively. A hybrid/hybridoma was established, and its bi-mAb was characterized. In combination with a costimulatory anti-CD28 mAb resting peripheral lymphocytes could be activated specifically with T-cell proliferation and secretion of high amounts of interferon-gamma. On specific T-cell activation, bi-mAb OKT3/NSI19-9 could also redirect the cytotoxic effects of these T cells toward CA19-9+ tumor cells in vitro. Our results indicate that specific activation of resting T cells with bi-mAb OKT3/NSI19-9 in combination with an anti-CD28 mAb can activate resting T cells specifically and leads to antigen-dependent bi-mAb-mediated cytotoxicity against CA19-9+ target cells. This approach may offer new perspectives for the specific immunotherapy of CA19-9+ tumors.
Hombach
A
A
Klinik I für Innere Medizin der Universität zu Köln, Germany.
Tillmann
T
T
Jensen
M
M
Heuser
C
C
Sircar
R
R
Diehl
V
V
Kruis
W
W
Pohl
C
C
D018033:Antibodies, Bispecific / Q000276:immunology* / Q000627:therapeutic use; D000911:Antibodies, Monoclonal / Q000276:immunology* / Q000627:therapeutic use; D000951:Antigens, Neoplasm / Q000276:immunology; D018395:CA-19-9 Antigen / Q000276:immunology*; D018106:CD28 Antigens / Q000276:immunology; D017252:CD3 Complex / Q000276:immunology; D015179:Colorectal Neoplasms / Q000276:immunology / Q000628:therapy; D005434:Flow Cytometry; D006801:Humans; D016219:Immunotherapy, Adoptive / Q000379:methods*; D008213:Lymphocyte Activation / Q000276:immunology; D016246:Lymphocytes, Tumor-Infiltrating / Q000276:immunology*; D016853:Muromonab-CD3 / Q000276:immunology / Q000627:therapeutic use; D014407:Tumor Cells, Cultured
D018033:Antibodies, Bispecific; D000911:Antibodies, Monoclonal; D000951:Antigens, Neoplasm; D018395:CA-19-9 Antigen; D018106:CD28 Antigens; D017252:CD3 Complex; D016853:Muromonab-CD3