Targeted therapy with a novel enediyene antibiotic calicheamicin theta(I)1 effectively suppresses growth and dissemination of liver metastases in a syngeneic model of murine neuroblastoma.
The suppression of metastases in malignant diseases is one of the major goals in targeted chemotherapy. This was achieved with an antibody drug conjugate between a novel, rationally designed enediyene antibiotic calicheamicin theta(I)1 of exceptionally high cytotoxic potency and an antiganglioside GD2 monoclonal antibody 14G2a. Effective suppression of hepatic metastases was demonstrated in a novel syngeneic model of murine neuroblastoma that simulates the situation in patients in terms of antigen heterogeneity and presence of the target antigen on normal tissues. Here, we describe the first successful use of calicheamicin theta(I)1 for targeted chemotherapy in a clinically relevant syngeneic metastasis model.
Department of Immunology, The Scripps Research Institute, La Jolla, California 92037, USA.
H N
HN
Lode
R A
RA
Reisfeld
R
R
Handgretinger
K C
KC
Nicolaou
G
G
Gaedicke
W
W
Wrasidlo
D000617:Aminoglycosides; D000818:Animals; D000900:Anti-Bacterial Agents / Q000009:adverse effects / Q000627:therapeutic use*; D000903:Antibiotics, Antineoplastic / Q000627:therapeutic use*; D000911:Antibodies, Monoclonal / Q000009:adverse effects / Q000627:therapeutic use*; D053281:Enediynes; D005732:Gangliosides / Q000276:immunology; D008113:Liver Neoplasms / Q000188:drug therapy / Q000556:secondary*; D051379:Mice; D009447:Neuroblastoma / Q000188:drug therapy* / Q000556:secondary; D014407:Tumor Cells, Cultured / Q000187:drug effects
D000617:Aminoglycosides; D000900:Anti-Bacterial Agents; D000903:Antibiotics, Antineoplastic; D000911:Antibodies, Monoclonal; D053281:Enediynes; D005732:Gangliosides; C113504:calicheamicin theta(1)I