scholarly journals Immunotherapy with immunocytokines and PD-1 blockade enhances the anticancer activity of Small Molecule-Drug Conjugates targeting Carbonic Anhydrase IX

2020 ◽  
pp. molcanther.0361.2020
Author(s):  
Jacopo Millul ◽  
Christiane Krudewig ◽  
Aureliano Zana ◽  
Sheila Dakhel Plaza ◽  
Emanuele Puca ◽  
...  
Keyword(s):  
Carbonic Anhydrase ◽  
Anticancer Activity ◽  
Small Molecule ◽  
Carbonic Anhydrase Ix ◽  
Small Molecule Drug ◽  
Drug Conjugates

scholarly journals Enhanced Therapeutic Activity of Non-Internalizing Small-Molecule-Drug Conjugates Targeting Carbonic Anhydrase IX in Combination with Targeted Interleukin-2

2018 ◽  
Vol 24 (15) ◽  
pp. 3656-3667 ◽  
Author(s):  
Samuele Cazzamalli ◽  
Barbara Ziffels ◽  
Fontaine Widmayer ◽  
Patrizia Murer ◽  
Giovanni Pellegrini ◽  
...  
Keyword(s):  
Carbonic Anhydrase ◽  
Small Molecule ◽  
Interleukin 2 ◽  
Carbonic Anhydrase Ix ◽  
Therapeutic Activity ◽  
Small Molecule Drug ◽  
Drug Conjugates

scholarly journals Immunotherapy with immunocytokines and PD-1 blockade enhances the anticancer activity of small molecule-drug conjugates targeting carbonic anhydrase IX

2020 ◽  
Author(s):  
Jacopo Millul ◽  
Christiane Krudewig ◽  
Aureliano Zana ◽  
Sheila Dakhel Plaza ◽  
Emanuele Puca ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Carbonic Anhydrase ◽  
Cell Carcinoma ◽  
Small Molecule ◽  
Renal Cell ◽  
Carbonic Anhydrase Ix ◽  
Therapeutic Window ◽  
Interleukin 12 ◽  
Small Molecule Drug ◽  
Drug Conjugates

AbstractSmall molecule-drug conjugates (SMDCs) represent an alternative to conventional antitumor chemotherapeutic agents, with the potential to improve the therapeutic window of cytotoxic payloads through active delivery at the site of the disease. In this article we describe novel combination therapies consisting of anti-Carbonic Anhydrase IX SMDCs combined with different immunomodulatory products. The therapeutic effect of the SMDCs was potentiated by combination with PD-1 blockade and with tumor-homing antibody-cytokine fusions in mouse models of renal cell carcinoma and colorectal cancer. The combination with L19-IL12, a fusion protein specific to the alternatively-spliced EDB domain of fibronectin containing the murine interleukin-12 moiety, was active also against large established tumors. Analysis of the microscopic structures of healthy organs performed three months after tumor eradication confirmed absence of pathological abnormalities in the healthy kidney, liver, lung, stomach and intestine. Our findings may be of clinical significance as they provide motivation for the development of combinations based on small molecule-drug conjugates and immunotherapy for the treatment of renal cell carcinoma and of hypoxic tumors.

A Small-Molecule Drug Conjugate for the Treatment of Carbonic Anhydrase IX Expressing Tumors

2014 ◽  
Vol 53 (16) ◽  
pp. 4231-4235 ◽  
Author(s):  
Nikolaus Krall ◽  
Francesca Pretto ◽  
Willy Decurtins ◽  
Gonçalo J. L. Bernardes ◽  
Claudiu T. Supuran ◽  
...  
Keyword(s):  
Carbonic Anhydrase ◽  
Small Molecule ◽  
Carbonic Anhydrase Ix ◽  
Drug Conjugate ◽  
Small Molecule Drug
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