Department of Chemistry, The Scripps Research Institute , 10550 North Torrey Pines Road, La Jolla, California 92037, United States.
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.
Written by:
Dubrovska A, Kim C, Elliott J, Shen W, Kuo TH, Koo DI, Li C, Tuntland T, Chang J, Groessl T, Wu X, Gorney V, Ramirez-Montagut T, Spiegel DA, Cho CY, Schultz PG. Are you the author?
Reference: ACS Chem Biol. 2011 Sep 21. Epub ahead of print.
doi: 10.1021/cb200222s
PubMed Abstract
PMID: 21936526
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