Journal
ACS CHEMICAL BIOLOGY
Volume 6, Issue 11, Pages 1223-1231Publisher
AMER CHEMICAL SOC
DOI: 10.1021/cb200222s
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Funding
- Susan G. Komen for the Cure [PDF0707903]
- Novartis Research Foundation
- Skaggs Institute for Chemical Biology
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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 (AD CC) 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.
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