Simultaneous activation of T cells and accessory cells by a new class of intact bispecific antibody results in efficient tumor cell killing.
Bispecific Abs (bsAb) are promising immunological tools for the elimination of tumor cells in minimal residual disease situations. In principle, they target an Ag on tumor cells and recruit one class of effector cell. Because immune reactions in vivo are more complex and are mediated by different classes of effector cell, we argue that conventional bsAb might not yield optimal immune responses at the tumor site. We therefore constructed a bsAb that combines the two potent effector subclasses mouse IgG2a and rat IgG2b. This bispecific molecule not only recruits T cells via its one binding arm, but simultaneously activates FcgammaR+ accessory cells via its Fc region. We demonstrate here that the activation of both T lymphocytes and accessory cells leads to production of immunomodulating cytokines like IL-1beta, IL-2, IL-6, IL-12, and DC-CK1. Thus this new class of bsAb elicits excellent antitumor activity in vitro even without the addition of exogenous IL-2, and therefore represents a totally self-supporting system.
Clinical Cooperation Group Bispecific Antibodies, Department of Otorhinolaryngology, Ludwig-Maximilians-University, Munich, Germany.
R
R
Zeidler
G
G
Reisbach
B
B
Wollenberg
S
S
Lang
S
S
Chaubal
B
B
Schmitt
H
H
Lindhofer
D000818:Animals; D018033:Antibodies, Bispecific / Q000737:chemistry / Q000235:genetics / Q000494:pharmacology*; D000920:Antibody-Dependent Cell Cytotoxicity / Q000276:immunology*; D000938:Antigen-Presenting Cells / Q000276:immunology* / Q000378:metabolism; D000951:Antigens, Neoplasm / Q000276:immunology / Q000502:physiology; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000276:immunology* / Q000494:pharmacology; D015815:Cell Adhesion Molecules / Q000276:immunology / Q000502:physiology; D002478:Cells, Cultured; D018920:Coculture Techniques; D016207:Cytokines / Q000096:biosynthesis; D003713:Dendritic Cells / Q000276:immunology; D000071858:Epithelial Cell Adhesion Molecule; D006801:Humans; D007376:Interleukin-2 / Q000096:biosynthesis; D008213:Lymphocyte Activation / Q000276:immunology*; D051379:Mice; D051381:Rats; D011993:Recombinant Fusion Proteins / Q000138:chemical synthesis / Q000276:immunology / Q000494:pharmacology; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D014407:Tumor Cells, Cultured
D018033:Antibodies, Bispecific; D000951:Antigens, Neoplasm; D000970:Antineoplastic Agents; D015815:Cell Adhesion Molecules; D016207:Cytokines; D000071858:Epithelial Cell Adhesion Molecule; D007376:Interleukin-2; D011993:Recombinant Fusion Proteins