Abstract
L19-tumor necrosis factor alpha (L19mTNF-α; L), a fusion protein consisting of mouse TNFα and the human antibody fragment L19 directed to the extra domain-B (ED-B) of fibronectin, is able to selectively target tumor vasculature and to exert a long-lasting therapeutic activity in combination with melphalan (M) in syngeneic mouse tumor models. We have studied the antitumor activity of single L19mTNF-α treatment in combination with melphalan and gemcitabine (G) using different administration protocols in two histologically different murine tumor models: WEHI-164 fibrosarcoma and K7M2 osteosarcoma. All responding mice showed significant reduction in myeloid-derived suppressor cells (MDSCs) and an increase in CD4+ and CD8+ T cells in the tumor infiltrates, as well as significant reduction in regulatory T cells (Treg) at the level of draining lymph nodes. What is important is that all cured mice rejected tumor challenge up to 1 year after therapy. Targeted delivery of L19mTNF-α synergistically increases the antitumor activity of melphalan and gemcitabine, but optimal administration schedules are required. This study provides information for designing clinical studies using L19mTNF-α in combination with chemotherapeutic drugs. Targeted delivery of L19mTNF-α synergistically increases the antitumor activity of melphalan and gemcitabine, but optimal administration schedule requires a pretreatment with L19mTNF-α otherwise an antagonistic effect could occur. This study provides information for designing clinical studies using L19mTNF-α in combination with chemotherapeutic drugs.
| Original language | English |
|---|---|
| Pages (from-to) | 478-487 |
| Number of pages | 10 |
| Journal | Cancer Medicine |
| Volume | 2 |
| Issue number | 4 |
| DOIs | |
| Publication status | Published - 2013 |
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ASJC Scopus subject areas
- Cancer Research
- Oncology
- Radiology Nuclear Medicine and imaging
Cite this
Schedule-dependent therapeutic efficacy of L19mTNF-α and melphalan combined with gemcitabine. / Mortara, Lorenzo; Orecchia, Paola; Castellani, Patrizia; Borsi, Laura; Carnemolla, Barbara; Balza, Enrica.
In: Cancer Medicine, Vol. 2, No. 4, 2013, p. 478-487.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Schedule-dependent therapeutic efficacy of L19mTNF-α and melphalan combined with gemcitabine
AU - Mortara, Lorenzo
AU - Orecchia, Paola
AU - Castellani, Patrizia
AU - Borsi, Laura
AU - Carnemolla, Barbara
AU - Balza, Enrica
PY - 2013
Y1 - 2013
N2 - L19-tumor necrosis factor alpha (L19mTNF-α; L), a fusion protein consisting of mouse TNFα and the human antibody fragment L19 directed to the extra domain-B (ED-B) of fibronectin, is able to selectively target tumor vasculature and to exert a long-lasting therapeutic activity in combination with melphalan (M) in syngeneic mouse tumor models. We have studied the antitumor activity of single L19mTNF-α treatment in combination with melphalan and gemcitabine (G) using different administration protocols in two histologically different murine tumor models: WEHI-164 fibrosarcoma and K7M2 osteosarcoma. All responding mice showed significant reduction in myeloid-derived suppressor cells (MDSCs) and an increase in CD4+ and CD8+ T cells in the tumor infiltrates, as well as significant reduction in regulatory T cells (Treg) at the level of draining lymph nodes. What is important is that all cured mice rejected tumor challenge up to 1 year after therapy. Targeted delivery of L19mTNF-α synergistically increases the antitumor activity of melphalan and gemcitabine, but optimal administration schedules are required. This study provides information for designing clinical studies using L19mTNF-α in combination with chemotherapeutic drugs. Targeted delivery of L19mTNF-α synergistically increases the antitumor activity of melphalan and gemcitabine, but optimal administration schedule requires a pretreatment with L19mTNF-α otherwise an antagonistic effect could occur. This study provides information for designing clinical studies using L19mTNF-α in combination with chemotherapeutic drugs.
AB - L19-tumor necrosis factor alpha (L19mTNF-α; L), a fusion protein consisting of mouse TNFα and the human antibody fragment L19 directed to the extra domain-B (ED-B) of fibronectin, is able to selectively target tumor vasculature and to exert a long-lasting therapeutic activity in combination with melphalan (M) in syngeneic mouse tumor models. We have studied the antitumor activity of single L19mTNF-α treatment in combination with melphalan and gemcitabine (G) using different administration protocols in two histologically different murine tumor models: WEHI-164 fibrosarcoma and K7M2 osteosarcoma. All responding mice showed significant reduction in myeloid-derived suppressor cells (MDSCs) and an increase in CD4+ and CD8+ T cells in the tumor infiltrates, as well as significant reduction in regulatory T cells (Treg) at the level of draining lymph nodes. What is important is that all cured mice rejected tumor challenge up to 1 year after therapy. Targeted delivery of L19mTNF-α synergistically increases the antitumor activity of melphalan and gemcitabine, but optimal administration schedules are required. This study provides information for designing clinical studies using L19mTNF-α in combination with chemotherapeutic drugs. Targeted delivery of L19mTNF-α synergistically increases the antitumor activity of melphalan and gemcitabine, but optimal administration schedule requires a pretreatment with L19mTNF-α otherwise an antagonistic effect could occur. This study provides information for designing clinical studies using L19mTNF-α in combination with chemotherapeutic drugs.
UR - http://www.scopus.com/inward/record.url?scp=84902081932&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84902081932&partnerID=8YFLogxK
U2 - 10.1002/cam4.89
DO - 10.1002/cam4.89
M3 - Article
C2 - 24156020
AN - SCOPUS:84902081932
VL - 2
SP - 478
EP - 487
JO - Cancer Medicine
JF - Cancer Medicine
SN - 2045-7634
IS - 4
ER -