Immune targeting of autocrine IGF2 hampers rhabdomyosarcoma growth and metastasis

Carla De Giovanni†View ORCID ID profile,
Patrizia Nanni†View ORCID ID profile,
Lorena Landuzzi†View ORCID ID profile,
Marianna L. IanzanoView ORCID ID profile,
Giordano NicolettiView ORCID ID profile,
Stefania CrociView ORCID ID profile,
Arianna Palladini†View ORCID ID profile and
Pier-Luigi Lollini†Email author View ORCID ID profile

†Contributed equally

BMC Cancer201919:126

https://doi.org/10.1186/s12885-019-5339-4

Received: 13 July 2018
Accepted: 31 January 2019
Published: 7 February 2019

Open Peer Review reports

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.