Preclinical Validation of a Single-Treatment Infusion Modality That Can Eradicate Extremity Melanomas.
Isolated limb perfusion (ILP) with the chemotherapeutic agent melphalan is an effective treatment option for extremity in-transit melanoma but is toxic and technically challenging to deliver locoregionally. CBL0137 is an experimental clinical drug with broad anticancer activity in animal models, owing to its ability to bind DNA in a nongenotoxic manner and inactivate the FACT chromatin modulator essential for tumor cell viability. Here, we report that CBL0137 delivered by ILP in a murine melanoma model is as efficacious as melphalan, displaying antitumor activity at doses corresponding to only a fraction of the systemic MTD of CBL0137. The ability to bind DNA quickly combined with a favorable safety profile made it possible to substitute CBL0137 in the ILP protocol, using an intra-arterial infusion method, to safely achieve effective tumor suppression. Our findings of a preclinical proof of concept for CBL0137 and its administration via intra-arterial infusion as a superior treatment compared with melphalan ILP allows for locoregional treatment anywhere a catheter can be placed. Cancer Res; 76(22); 6620-30. ©2016 AACR.
Department of Surgical Oncology, Roswell Park Cancer Institute, Buffalo, New York.|Department of Immunology, Roswell Park Cancer Institute, Buffalo, New York.
Minhyung
M
Kim
Department of Cell Stress Biology, Roswell Park Cancer Institute, Buffalo, New York.
Nickolay
N
Neznanov
Department of Surgical Oncology, Roswell Park Cancer Institute, Buffalo, New York.
Chandler D
CD
Wilfong
Department of Cell Stress Biology, Roswell Park Cancer Institute, Buffalo, New York.
Daria I
DI
Fleyshman
Cleveland BioLabs, Inc., Buffalo, New York.|Incuron, LLC, Buffalo, New York.
Andrei A
AA
Purmal
Buffalo BioLabs, LLC, Buffalo, New York.
Gary
G
Haderski
Buffalo BioLabs, LLC, Buffalo, New York.
Patricia
P
Stanhope-Baker
Buffalo BioLabs, LLC, Buffalo, New York.
Catherine A
CA
Burkhart
Department of Cell Stress Biology, Roswell Park Cancer Institute, Buffalo, New York.
Katerina V
KV
Gurova
Department of Cell Stress Biology, Roswell Park Cancer Institute, Buffalo, New York.
Andrei V
AV
Gudkov
Department of Surgical Oncology, Roswell Park Cancer Institute, Buffalo, New York. joseph.skitzki@roswellpark.org.|Department of Immunology, Roswell Park Cancer Institute, Buffalo, New York.
Joseph J
JJ
Skitzki
D000818:Animals; D005121:Extremities / Q000473:pathology*; D005260:Female; D006801:Humans; D007260:Infusion Pumps; D008545:Melanoma / Q000188:drug therapy* / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D016896:Treatment Outcome; D054928:Validation Studies as Topic
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