Immune targeting of autocrine IGF2 hampers rhabdomyosarcoma growth and metastasis

Carla De Giovanni, Patrizia Nanni, Lorena Landuzzi, Marianna L Ianzano, Giordano Nicoletti, Stefania Croci, Arianna Palladini, Pier-Luigi Lollini

Research output: Contribution to journalArticle

Abstract

BACKGROUND: Insulin-like Growth Factor Receptor-1 (IGF1R) system sustains the genesis of rhabdomyosarcoma through IGF2 autocrine overexpression. While several IGF1R-targeted strategies have been investigated to interphere with rhabdomyosarcoma growth, no attempt to neutralize IGF2 has been reported. We therefore studied the possibility to hamper rhabdomyosarcoma growth with passive and active immune approaches targeting IGF2.

METHODS: A murine model developing IGF2-overexpressing pelvic rhabdomyosarcoma, along with IGF2-independent salivary carcinoma, was used to investigate the efficacy and specificity of passive anti-IGFs antibody treatment. Active vaccinations with electroporated DNA plasmids encoding murine or human IGF2 were performed to elicit autochthonous anti-IGF2 antibodies. Vaccinated mice received the intravenous injection of rhabdomyosarcoma cells to study the effects of anti-IGF2 antibodies against developing metastases.

RESULTS: Passive administration of antibodies neutralizing IGFs delayed the onset of IGF2-overexpressing rhabdomyosarcoma but not of IGF2-independent salivary carcinoma. A DNA vaccine against murine IGF2 did not elicit antibodies, even when combined with Treg-depletion, while a DNA vaccine encoding the human IGF2 gene elicited antibodies crossreacting with murine IGF2. Mice with anti-IGF2 antibodies were partially protected against the metastatic growth of IGF2-addicted rhabdomyosarcoma cells.

CONCLUSIONS: Immune targeting of autocrine IGF2 inhibited rhabdomyosarcoma genesis and metastatic growth.

Original languageEnglish
Pages (from-to)1-7
Number of pages7
JournalBMC Cancer
Volume19
Issue number1
DOIs
Publication statusPublished - Feb 7 2019

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Rhabdomyosarcoma
Neoplasm Metastasis
Growth
Anti-Idiotypic Antibodies
DNA Vaccines
Carcinoma
Somatomedin Receptors
Antibodies
Neutralizing Antibodies
Intravenous Injections
Vaccination
Plasmids
DNA

Keywords

  • DNA vaccines
  • IGF1R
  • IGF2
  • Immunoprevention
  • Neutralizing antibodies
  • Rhabdomyosarcoma

Cite this

Immune targeting of autocrine IGF2 hampers rhabdomyosarcoma growth and metastasis. / De Giovanni, Carla; Nanni, Patrizia; Landuzzi, Lorena; Ianzano, Marianna L; Nicoletti, Giordano; Croci, Stefania; Palladini, Arianna; Lollini, Pier-Luigi.

In: BMC Cancer, Vol. 19, No. 1, 07.02.2019, p. 1-7.

Research output: Contribution to journalArticle

De Giovanni, C, Nanni, P, Landuzzi, L, Ianzano, ML, Nicoletti, G, Croci, S, Palladini, A & Lollini, P-L 2019, 'Immune targeting of autocrine IGF2 hampers rhabdomyosarcoma growth and metastasis', BMC Cancer, vol. 19, no. 1, pp. 1-7. https://doi.org/10.1186/s12885-019-5339-4
De Giovanni, Carla ; Nanni, Patrizia ; Landuzzi, Lorena ; Ianzano, Marianna L ; Nicoletti, Giordano ; Croci, Stefania ; Palladini, Arianna ; Lollini, Pier-Luigi. / Immune targeting of autocrine IGF2 hampers rhabdomyosarcoma growth and metastasis. In: BMC Cancer. 2019 ; Vol. 19, No. 1. pp. 1-7.
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AU - Nicoletti, Giordano

AU - Croci, Stefania

AU - Palladini, Arianna

AU - Lollini, Pier-Luigi

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N2 - BACKGROUND: Insulin-like Growth Factor Receptor-1 (IGF1R) system sustains the genesis of rhabdomyosarcoma through IGF2 autocrine overexpression. While several IGF1R-targeted strategies have been investigated to interphere with rhabdomyosarcoma growth, no attempt to neutralize IGF2 has been reported. We therefore studied the possibility to hamper rhabdomyosarcoma growth with passive and active immune approaches targeting IGF2.METHODS: A murine model developing IGF2-overexpressing pelvic rhabdomyosarcoma, along with IGF2-independent salivary carcinoma, was used to investigate the efficacy and specificity of passive anti-IGFs antibody treatment. Active vaccinations with electroporated DNA plasmids encoding murine or human IGF2 were performed to elicit autochthonous anti-IGF2 antibodies. Vaccinated mice received the intravenous injection of rhabdomyosarcoma cells to study the effects of anti-IGF2 antibodies against developing metastases.RESULTS: Passive administration of antibodies neutralizing IGFs delayed the onset of IGF2-overexpressing rhabdomyosarcoma but not of IGF2-independent salivary carcinoma. A DNA vaccine against murine IGF2 did not elicit antibodies, even when combined with Treg-depletion, while a DNA vaccine encoding the human IGF2 gene elicited antibodies crossreacting with murine IGF2. Mice with anti-IGF2 antibodies were partially protected against the metastatic growth of IGF2-addicted rhabdomyosarcoma cells.CONCLUSIONS: Immune targeting of autocrine IGF2 inhibited rhabdomyosarcoma genesis and metastatic growth.

AB - BACKGROUND: Insulin-like Growth Factor Receptor-1 (IGF1R) system sustains the genesis of rhabdomyosarcoma through IGF2 autocrine overexpression. While several IGF1R-targeted strategies have been investigated to interphere with rhabdomyosarcoma growth, no attempt to neutralize IGF2 has been reported. We therefore studied the possibility to hamper rhabdomyosarcoma growth with passive and active immune approaches targeting IGF2.METHODS: A murine model developing IGF2-overexpressing pelvic rhabdomyosarcoma, along with IGF2-independent salivary carcinoma, was used to investigate the efficacy and specificity of passive anti-IGFs antibody treatment. Active vaccinations with electroporated DNA plasmids encoding murine or human IGF2 were performed to elicit autochthonous anti-IGF2 antibodies. Vaccinated mice received the intravenous injection of rhabdomyosarcoma cells to study the effects of anti-IGF2 antibodies against developing metastases.RESULTS: Passive administration of antibodies neutralizing IGFs delayed the onset of IGF2-overexpressing rhabdomyosarcoma but not of IGF2-independent salivary carcinoma. A DNA vaccine against murine IGF2 did not elicit antibodies, even when combined with Treg-depletion, while a DNA vaccine encoding the human IGF2 gene elicited antibodies crossreacting with murine IGF2. Mice with anti-IGF2 antibodies were partially protected against the metastatic growth of IGF2-addicted rhabdomyosarcoma cells.CONCLUSIONS: Immune targeting of autocrine IGF2 inhibited rhabdomyosarcoma genesis and metastatic growth.

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