Paclitaxel enhances therapeutic efficacy of the F8-IL2 immunocytokine to EDA-fibronectin-positive metastatic human melanoma xenografts

Michele Moschetta, Francesca Pretto, Alexander Berndt, Kerstin Galler, Petra Richter, Andrea Bassi, Paolo Oliva, Edoardo Micotti, Giovanni Valbusa, Kathrin Schwager, Manuela Kaspar, Eveline Trachsel, Hartwig Kosmehl, Maria Rosa Bani, Dario Neri, Raffaella Giavazzi

Research output: Contribution to journalArticle

Abstract

The selective delivery of bioactive agents to tumors reduces toxicity and enhances the efficacy of anticancer therapies. In this study, we show that the antibody F8, which recognizes perivascular and stromal EDA-fibronectin (EDA-Fn), when conjugated to interleukin-2 (F8-IL2) can effectively inhibit the growth of EDA-Fn-expressing melanomas in combination with paclitaxel. We obtained curative effects with paclitaxel administered before the immunocytokine. Coadministration of paclitaxel increased the uptake of F8 in xenografted melanomas, enhancing tumor perfusion and permeability. Paclitaxel also boosted the recruitment of F8-IL2-induced natural killer (NK) cells to the tumor, suggesting a host response as part of the observed therapeutic benefit. In support of this likelihood, NK cell depletion impaired the antitumor effect of paclitaxel plus F8-IL2. Importantly, this combination reduced both the tumor burden and the number of pulmonary metastatic nodules. The combination did not cause cumulative toxicity. Together, our findings offer a preclinical proof that by acting on the tumor stroma paclitaxel potentiates the antitumor activity elicited by a targeted delivery of IL2, thereby supporting the use of immunochemotherapy in the treatment of metastatic melanoma.

Original languageEnglish
Pages (from-to)1814-1824
Number of pages11
JournalCancer Research
Volume72
Issue number7
DOIs
Publication statusPublished - Apr 1 2012

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Paclitaxel
Fibronectins
Heterografts
Melanoma
Interleukin-2
Natural Killer Cells
Neoplasms
Therapeutics
Tumor Burden
F8-IL2 immunocytokine
Permeability
Perfusion
Lung
Growth

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Paclitaxel enhances therapeutic efficacy of the F8-IL2 immunocytokine to EDA-fibronectin-positive metastatic human melanoma xenografts. / Moschetta, Michele; Pretto, Francesca; Berndt, Alexander; Galler, Kerstin; Richter, Petra; Bassi, Andrea; Oliva, Paolo; Micotti, Edoardo; Valbusa, Giovanni; Schwager, Kathrin; Kaspar, Manuela; Trachsel, Eveline; Kosmehl, Hartwig; Bani, Maria Rosa; Neri, Dario; Giavazzi, Raffaella.

In: Cancer Research, Vol. 72, No. 7, 01.04.2012, p. 1814-1824.

Research output: Contribution to journalArticle

Moschetta, M, Pretto, F, Berndt, A, Galler, K, Richter, P, Bassi, A, Oliva, P, Micotti, E, Valbusa, G, Schwager, K, Kaspar, M, Trachsel, E, Kosmehl, H, Bani, MR, Neri, D & Giavazzi, R 2012, 'Paclitaxel enhances therapeutic efficacy of the F8-IL2 immunocytokine to EDA-fibronectin-positive metastatic human melanoma xenografts', Cancer Research, vol. 72, no. 7, pp. 1814-1824. https://doi.org/10.1158/0008-5472.CAN-11-1919
Moschetta, Michele ; Pretto, Francesca ; Berndt, Alexander ; Galler, Kerstin ; Richter, Petra ; Bassi, Andrea ; Oliva, Paolo ; Micotti, Edoardo ; Valbusa, Giovanni ; Schwager, Kathrin ; Kaspar, Manuela ; Trachsel, Eveline ; Kosmehl, Hartwig ; Bani, Maria Rosa ; Neri, Dario ; Giavazzi, Raffaella. / Paclitaxel enhances therapeutic efficacy of the F8-IL2 immunocytokine to EDA-fibronectin-positive metastatic human melanoma xenografts. In: Cancer Research. 2012 ; Vol. 72, No. 7. pp. 1814-1824.
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