A Chemically Induced Vaccine Strategy for Prostate Cancer

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 i...

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Bibliographic Details
Published in:ACS chemical biology 2011-11, Vol.6 (11), p.1223-1231
Main Authors: Dubrovska, Anna, Kim, Chanhyuk, Elliott, Jimmy, Shen, Weijun, Kuo, Tun-Hsun, Koo, Dong-In, Li, Chun, Tuntland, Tove, Chang, Jonathan, Groessl, Todd, Wu, Xu, Gorney, Vanessa, Ramirez-Montagut, Teresa, Spiegel, David A, Cho, Charles Y, Schultz, Peter G
Format: Article
Language:English
Subjects:
2,4-Dinitrophenol - chemistry
2,4-Dinitrophenol - immunology
Animals
Antibodies, Neoplasm - immunology
Antibody-Dependent Cell Cytotoxicity - drug effects
Antibody-Dependent Cell Cytotoxicity - immunology
Antigens, Neoplasm - immunology
Antigens, Surface - metabolism
Autoantigens - immunology
Cancer Vaccines - chemistry
Cancer Vaccines - immunology
Cancer Vaccines - therapeutic use
Cell Proliferation - drug effects
Cell Survival - drug effects
Drug Screening Assays, Antitumor
Glutamate Carboxypeptidase II - metabolism
Humans
Ligands
Male
Mice
Mice, Inbred C57BL
Mice, Inbred NOD
Mice, SCID
Prostatic Neoplasms - immunology
Prostatic Neoplasms - pathology
Prostatic Neoplasms - therapy
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Summary: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.
ISSN:1554-8929
1554-8937
DOI:10.1021/cb200222s