Anti-CD166 single chain antibody-mediated intracellular delivery of liposomal drugs to prostate cancer cells.
Targeted delivery of small-molecule drugs has the potential to enhance selective killing of tumor cells. We have identified previously an internalizing single chain [single chain variable fragment (scFv)] antibody that targets prostate cancer cells and identified the target antigen as CD166. We report here the development of immunoliposomes using this anti-CD166 scFv (H3). We studied the effects of a panel of intracellularly delivered, anti-CD166 immunoliposomal small-molecule drugs on prostate cancer cells. Immunoliposomal formulations of topotecan, vinorelbine, and doxorubicin each showed efficient and targeted uptake by three prostate cancer cell lines (Du-145, PC3, and LNCaP). H3-immunoliposomal topotecan was the most effective in cytotoxicity assays on all three tumor cell lines, showing improved cytotoxic activity compared with nontargeted liposomal topotecan. Other drugs such as liposomal doxorubicin were highly effective against LNCaP but not PC3 or Du-145 cells, despite efficient intracellular delivery. Post-internalization events thus modulate the overall efficacy of intracellularly delivered liposomal drugs, contributing in some cases to the lower than expected activity in a cell line-dependent manner. Further studies on intracellular tracking of endocytosed liposomal drugs will help identify and overcome the barriers limiting the potency of liposomal drugs.
Roth
Audrey
A
Department of Anesthesia, University of California at San Francisco, Room 3C38, 1001 Potrero Avenue, San Francisco, CA 94110, USA.
Drummond
Daryl C
DC
Conrad
Fraser
F
Hayes
Mark E
ME
Kirpotin
Dmitri B
DB
Benz
Christopher C
CC
Marks
James D
JD
Liu
Bin
B
D020410:Activated-Leukocyte Cell Adhesion Molecule / Q000276:immunology*; D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage; D000911:Antibodies, Monoclonal / Q000008:administration & dosage*; D000970:Antineoplastic Agents / Q000008:administration & dosage; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage; D002450:Cell Communication / Q000276:immunology; D045744:Cell Line, Tumor / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004317:Doxorubicin / Q000008:administration & dosage; D016503:Drug Delivery Systems; D005434:Flow Cytometry; D006801:Humans; D007128:Immunoglobulin Fragments / Q000276:immunology; D008024:Ligands; D008081:Liposomes; D008297:Male; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000473:pathology; D011838:Radiation-Sensitizing Agents / Q000008:administration & dosage; D019772:Topotecan / Q000008:administration & dosage; D014747:Vinblastine / Q000008:administration & dosage / Q000031:analogs & derivatives; D000077235:Vinorelbine
D020410:Activated-Leukocyte Cell Adhesion Molecule; D000903:Antibiotics, Antineoplastic; D000911:Antibodies, Monoclonal; D000970:Antineoplastic Agents; D000972:Antineoplastic Agents, Phytogenic; D007128:Immunoglobulin Fragments; D008024:Ligands; D008081:Liposomes; D011838:Radiation-Sensitizing Agents; D014747:Vinblastine; D019772:Topotecan; D004317:Doxorubicin; D000077235:Vinorelbine