Enhancing Natural Killer and CD8+ T Cell-Mediated Anticancer Cytotoxicity and Proliferation of CD8+ T Cells with HLA-E Monospecific Monoclonal Antibodies.

Enhancing Natural Killer and CD8+ T Cell-Mediated Anticancer Cytotoxicity and Proliferation of CD8+ T Cells with HLA-E Monospecific Monoclonal Antibodies. Monoclon Antib Immunodiagn Immunother. 2019 Apr;38(2):38-59 Authors: Ravindranath MH, Filippone EJ, Devarajan A, Asgharzadeh S Abstract Cytotoxic NK/CD8+ T cells interact with MHC-I ligands on tumor cells through either activating or inhibiting receptors. One of the inhibitory receptors is CD94/NKG2A. The NK/CD8+ T cell cytotoxic capability is lost when tumor-associated human leukocyte antigen, HLA-E, binds the CD94/NKG2A receptor, resulting in tumor progression and reduced survival. Failure of cancer patients to respond to natural killer (NK) cell therapies could be due to HLA-E overexpression in tumor tissues. Preventing the inhibitory receptor-ligand interaction by either receptor- or ligand-specific monoclonal antibodies (mAbs) is an innovative passive immunotherapeutic strategy for cancer. Since receptors and ligands can be monomeric or homo- or heterodimeric proteins, the efficacy of mAbs may rely on their ability to distinguish monospecific (private) functional epitopes from nonfunctional common (public) epitopes. We developed monospecific anti-HLA-E mAbs (e.g., TFL-033) that recognize only HLA-E-specific epitopes, but not epitopes shared with other HLA class-I loci as occurs with currently available polyreactive anti-HLA-E mAbs. Interestingly the amino acid sequences in the...
Source: Monoclonal Antibodies in Immunodiagnosis and Immunotherapy - Category: Microbiology Tags: Monoclon Antib Immunodiagn Immunother Source Type: research