Cell-targeting fusion constructs containing recombinant gelonin.
Therapeutic agents capable of targeting tumor cells present as established tumors and micrometastases have already demonstrated their potential in clinical trials. Immunotoxins targeting hematological malignancies and solid tumors have additionally demonstrated excellent clinical activity. This review focuses on our design and characterization studies of constructs composed of recombinant gelonin toxin fused to either growth factors or single-chain antibodies targeting solid tumor cells, tumor vasculature or hematological malignancies. These agents demonstrate cytotoxicity at nanomolar or sub-nanomolar levels. All of these constructs display impressive selectivity and specificity for antigen-bearing target cells in vitro and in vivo and are excellent clinical trial candidates.
Immunopharmacology and Targeted Therapy Laboratory, Department of Experimental Therapeutics, M.D. Anderson Cancer Center, Houston, Texas, USA.
Mi-Ae
MA
Lyu
Yu Joshua
YJ
Cao
Khalid A
KA
Mohamedali
Michael G
MG
Rosenblum
D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000276:immunology / Q000494:pharmacology; D001402:B-Lymphocytes / Q000187:drug effects / Q000276:immunology / Q000473:pathology; D002642:Chick Embryo; D049033:Chorioallantoic Membrane / Q000098:blood supply* / Q000187:drug effects / Q000378:metabolism; D000939:Epitopes; D006801:Humans; D007128:Immunoglobulin Fragments / Q000235:genetics / Q000276:immunology* / Q000494:pharmacology; D000922:Immunotoxins / Q000235:genetics / Q000276:immunology* / Q000494:pharmacology; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics / Q000276:immunology* / Q000494:pharmacology; D051379:Mice; D008819:Mice, Nude; D058990:Molecular Targeted Therapy / Q000379:methods; D009369:Neoplasms / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D009389:Neovascularization, Pathologic; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000276:immunology / Q000494:pharmacology; D054789:Ribosome Inactivating Proteins, Type 1 / Q000235:genetics / Q000276:immunology* / Q000494:pharmacology; D057127:Single-Chain Antibodies / Q000235:genetics / Q000276:immunology* / Q000494:pharmacology; D014407:Tumor Cells, Cultured; D023041:Xenograft Model Antitumor Assays
D000972:Antineoplastic Agents, Phytogenic; D000939:Epitopes; D007128:Immunoglobulin Fragments; D000922:Immunotoxins; D036341:Intercellular Signaling Peptides and Proteins; D011993:Recombinant Fusion Proteins; D054789:Ribosome Inactivating Proteins, Type 1; D057127:Single-Chain Antibodies; C025674:GEL protein, Gelonium multiflorum