Subject(s)
Folate Receptors, GPI-Anchored/metabolism , T-Lymphocytes, Cytotoxic/immunology , Animals , CD3 Complex/immunology , Cell Line, Tumor , Coculture Techniques , Folic Acid/chemistry , Humans , Immunoglobulin Fab Fragments/chemistry , Immunoglobulin Fab Fragments/immunology , Immunoglobulin Fc Fragments/chemistry , Immunoglobulin Fc Fragments/immunology , Immunoglobulin G/chemistry , Immunoglobulin G/immunology , Immunotherapy , Leukocytes, Mononuclear/cytology , Male , Mice , Mice, Inbred NOD , Mice, SCID , Neoplasms/metabolism , Neoplasms/pathology , Neoplasms/therapy , Rats , Rats, Sprague-Dawley , T-Lymphocytes, Cytotoxic/cytologyABSTRACT
Here we report the design and evaluation of a bifunctional, small molecule switch that induces a targeted immune response against tumors in vivo. A high affinity ligand for prostate specific membrane antigen (PSMA) was conjugated to a hapten that binds dinitrophenyl (DNP)-specific antibodies. When introduced into hu-PBL-NOD/SCID mice previously immunized with a KLH-DNP immunogen, this conjugate induced a targeted antibody-dependent cellular cytotoxicity (ADCC) response to PSMA-expressing tumor cells in a mouse xenograft model. The ability to create a small molecule inducible antibody response against self-antigens using endogenous non-autoreactive antibodies may provide advantages over the autologous immune response generated by conventional vaccines in certain therapeutic settings.
