Synthesis and in vitro testing of J591 antibody-dendrimer conjugates for targeted prostate cancer therapy.
Targeted therapeutics using antibodies are an attractive option over conventional cancer chemotherapeutics due to their potential to deliver a therapeutic specifically to cancer tissue without damaging normal tissue. However, there are known problems with immunoconjugates such as decreased immunoreactivity and poor solubility. Using dendrimers as carriers for these agents has the potential to resolve these issues. We synthesized J591 anti-PSMA (prostate specific membrane antigen) antibody dendrimer conjugates containing fluorophores on the dendrimer. The in vitro studies of these conjugates show that they specifically bind to cells expressing PSMA. Confocal microscopy experiments document the binding and internalization of these conjugates. This research encourages the further study of antibody-dendrimer-drug conjugates for use in targeted therapeutics.
Patri
Anil K
AK
Center for Biologic Nanotechnology, Department of Internal Medicine, Division of Allergy, University of Michigan, 9220 MSRB III, Box 0648, Ann Arbor, Michigan 48109, USA.
Myc
Andrzej
A
Beals
James
J
Thomas
Thommey P
TP
Bander
Neil H
NH
Baker
James R
JR
D000911:Antibodies, Monoclonal / Q000737:chemistry* / Q000378:metabolism* / Q000627:therapeutic use; D045744:Cell Line, Tumor; D016503:Drug Delivery Systems / Q000379:methods*; D006801:Humans; D008297:Male; D011471:Prostatic Neoplasms / Q000188:drug therapy / Q000276:immunology / Q000378:metabolism*; D011485:Protein Binding / Q000187:drug effects / Q000502:physiology
D000911:Antibodies, Monoclonal; C478680:J591 monoclonal antibody