TY - JOUR
T1 - Therapy-induced antitumor vaccination in neuroblastomas by the combined targeting of IL-2 and TNFα
AU - Balza, Enrica
AU - Carnemolla, Barbara
AU - Mortara, Lorenzo
AU - Castellani, Patrizia
AU - Soncini, Debora
AU - Accolla, Roberto S.
AU - Borsi, Laura
PY - 2010/7/1
Y1 - 2010/7/1
N2 - L19-IL2 and L19TNFα are fusion proteins composed of L19(scFv), specific for the angiogenesis-associated ED-B containing fibronectin isoform and IL-2 or TNFa. Because of the tumor targeting properties of L19, IL-2 and TNFa concentrate at therapeutic doses at the tumor vascular level. To evaluate the therapeutic effects of L19-IL2 and L19mTNFa in neuroblastoma (NB)-bearing mice, A/J mice bearing Neuro2A or NIE115 NB were systemically treated with L19-IL2 and L19mTNFα, alone or in combination protocols. Seventy percent of Neuro2A- and 30% of NIE115-bearing mice were cured by the combined treatment with L19-IL2 and L19mTNFα, and further rejected a homologous tumor challenge, indicating specific antitumor immune memory. The immunological bases of tumor cure and rejection were studied. A highly efficient priming of CD4
+ T helper cells and CD8
+ CTL effectors was generated, paralleled by massive infiltration in the tumor tissue of CD4
+ and CD8
+ T cells at day 16 after tumor cell implantation, when, after therapy, tumor volume was drastically reduced and tumor necrosis reached about 80%. The curative treatment resulted in a long-lasting antitumor immune memory, accompanied by a mixed Th1/Th2 type of response. Concluding, L19-IL2 and L19mTNFα efficiently cooperate in determining a high percentage of NB cure that, in our experimental models, is strongly associated to the generation of adaptive immunity involving CD4
+ and CD8
+ T cells.
AB - L19-IL2 and L19TNFα are fusion proteins composed of L19(scFv), specific for the angiogenesis-associated ED-B containing fibronectin isoform and IL-2 or TNFa. Because of the tumor targeting properties of L19, IL-2 and TNFa concentrate at therapeutic doses at the tumor vascular level. To evaluate the therapeutic effects of L19-IL2 and L19mTNFa in neuroblastoma (NB)-bearing mice, A/J mice bearing Neuro2A or NIE115 NB were systemically treated with L19-IL2 and L19mTNFα, alone or in combination protocols. Seventy percent of Neuro2A- and 30% of NIE115-bearing mice were cured by the combined treatment with L19-IL2 and L19mTNFα, and further rejected a homologous tumor challenge, indicating specific antitumor immune memory. The immunological bases of tumor cure and rejection were studied. A highly efficient priming of CD4
+ T helper cells and CD8
+ CTL effectors was generated, paralleled by massive infiltration in the tumor tissue of CD4
+ and CD8
+ T cells at day 16 after tumor cell implantation, when, after therapy, tumor volume was drastically reduced and tumor necrosis reached about 80%. The curative treatment resulted in a long-lasting antitumor immune memory, accompanied by a mixed Th1/Th2 type of response. Concluding, L19-IL2 and L19mTNFα efficiently cooperate in determining a high percentage of NB cure that, in our experimental models, is strongly associated to the generation of adaptive immunity involving CD4
+ and CD8
+ T cells.
KW - Angiogenesis
KW - Immunotherapy
KW - Neuroblastoma
KW - Oncofetal fibronectin
KW - Tumor targeting
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U2 - 10.1002/ijc.25018
DO - 10.1002/ijc.25018
M3 - Article
C2 - 19877124
AN - SCOPUS:77953445215
VL - 127
SP - 101
EP - 110
JO - International Journal of Cancer
JF - International Journal of Cancer
SN - 0020-7136
IS - 1
ER -