TY - JOUR
T1 - L19-IL2 immunocytokine in combination with the anti-syndecan-1 46F2SIP antibody format
T2 - A new targeted treatment approach in an ovarian carcinoma model
AU - Orecchia, Paola
AU - Balza, Enrica
AU - Pietra, Gabriella
AU - Conte, Romana
AU - Bizzarri, Nicolò
AU - Ferrero, Simone
AU - Mingari, Maria Cristina
AU - Carnemolla, Barbara
PY - 2019/9/1
Y1 - 2019/9/1
N2 - Epithelial ovarian cancer (EOC) is the fifth most common cancer affecting the female population. At present, different targeted treatment approaches may improve currently employed therapies leading either to the delay of tumor recurrence or to disease stabilization. In this study we show that syndecan-1 (SDC1) and tumor angiogenic-associated B-fibronectin isoform (B-FN) are involved in EOC progression and we describe the prominent role of SDC1 in the vasculogenic mimicry (VM) process. We also investigate a possible employment of L19-IL2, an immunocytokine specific for B-FN, and anti-SDC1 46F2SIP (small immuno protein) antibody in combination therapy in a human ovarian carcinoma model. A tumor growth reduction of 78% was obtained in the 46F2SIP/L19-IL2-treated group compared to the control group. We observed that combined treatment was effective in modulation of epithelial-mesenchymal transition (EMT) markers, loss of stemness properties of tumor cells, and in alleviating hypoxia. These effects correlated with reduction of VM structures in tumors from treated mice. Interestingly, the improved pericyte coverage in vascular structures suggested that combined therapy could be efficacious in induction of vessel normalization. These data could pave the way for a possible use of L19-IL2 combined with 46F2SIP antibody as a novel therapeutic strategy in EOC.
AB - Epithelial ovarian cancer (EOC) is the fifth most common cancer affecting the female population. At present, different targeted treatment approaches may improve currently employed therapies leading either to the delay of tumor recurrence or to disease stabilization. In this study we show that syndecan-1 (SDC1) and tumor angiogenic-associated B-fibronectin isoform (B-FN) are involved in EOC progression and we describe the prominent role of SDC1 in the vasculogenic mimicry (VM) process. We also investigate a possible employment of L19-IL2, an immunocytokine specific for B-FN, and anti-SDC1 46F2SIP (small immuno protein) antibody in combination therapy in a human ovarian carcinoma model. A tumor growth reduction of 78% was obtained in the 46F2SIP/L19-IL2-treated group compared to the control group. We observed that combined treatment was effective in modulation of epithelial-mesenchymal transition (EMT) markers, loss of stemness properties of tumor cells, and in alleviating hypoxia. These effects correlated with reduction of VM structures in tumors from treated mice. Interestingly, the improved pericyte coverage in vascular structures suggested that combined therapy could be efficacious in induction of vessel normalization. These data could pave the way for a possible use of L19-IL2 combined with 46F2SIP antibody as a novel therapeutic strategy in EOC.
KW - 46F2SIP anti-syndecan-1
KW - Angiogenesis
KW - L19-IL2 immunocytokine
KW - Ovarian cancer
KW - Syndecan-1 (SDC1)
KW - Targeted therapy
KW - Vascular mimicry
KW - Vessels normalization
UR - http://www.scopus.com/inward/record.url?scp=85071837424&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85071837424&partnerID=8YFLogxK
U2 - 10.3390/cancers11091232
DO - 10.3390/cancers11091232
M3 - Article
AN - SCOPUS:85071837424
VL - 11
JO - Cancers
JF - Cancers
SN - 2072-6694
IS - 9
M1 - 1232
ER -