Cancer vaccines co-targeting HER2/NEU and IGF1R

Carla De Giovanni, Lorena Landuzzi, Arianna Palladini, Marianna Lucia Ianzano, Giordano Nicoletti, Francesca Ruzzi, Augusto Amici, Stefania Croci, Patrizia Nanni, Pier Luigi Lollini

Research output: Contribution to journalArticle

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Abstract

(1) Background: Human epidermal growth factor receptor 2 (HER2)/neu-driven carcinogenesis is delayed by preventive vaccines able to elicit autochthonous antibodies against HER2/neu. Since cooperation between different receptor tyrosine kinases (RTKs) can occur in human as well as in experimental tumors, we investigated the set-up of DNA and cell vaccines to elicit an antibody response co-targeting two RTKs: HER2/neu and the Insulin-like Growth Factor Receptor-1 (IGF1R). (2) Methods: Plasmid vectors carrying the murine optimized IGF1R sequence or the human IGF1R isoform were used as electroporated DNA vaccines. IGF1R plasmids were transfected in allogeneic HER2/neu-positive IL12-producing murine cancer cells to obtain adjuvanted cell vaccines co-expressing HER2/neu and IGF1R. Vaccination was administered in the preneoplastic stage to mice prone to develop HER2/neu-driven, IGF1R-dependent rhabdomyosarcoma. (3) Results: Electroporated DNA vaccines for murine IGF1R did not elicit anti-mIGF1R antibodies, even when combined with Treg-depletion and/or IL12, while DNA vaccines carrying the human IGF1R elicited antibodies recognizing only the human IGF1R isoform. Cell vaccines co-expressing HER2/neu and murine or human IGF1R succeeded in eliciting antibodies recognizing the murine IGF1R isoform. Cell vaccines co-targeting HER2/neu and murine IGF1R induced the highest level of anti-IGF1R antibodies and nearly significantly delayed the onset of spontaneous rhabdomyosarcomas. (4) Conclusions: Multi-engineered adjuvanted cancer cell vaccines can break the tolerance towards a highly tolerized RTK, such as IGF1R. Cell vaccines co-targeting HER2/neu and IGF1R elicited low levels of specific antibodies that slightly delayed onset of HER2/neu-driven, IGF1R-dependent tumors.

Original languageEnglish
Article number517
JournalCancers
Volume11
Issue number4
DOIs
Publication statusPublished - Apr 1 2019

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Cancer Vaccines
DNA Vaccines
Vaccines
Receptor Protein-Tyrosine Kinases
Protein Isoforms
Rhabdomyosarcoma
Antibodies
Interleukin-12
Anti-Idiotypic Antibodies
Plasmids
human ERBB2 protein
Somatomedin Receptors
Neoplasms
Antibody Formation
Carcinogenesis
Vaccination

Keywords

  • Cancer vaccines
  • DNA vaccines
  • HER2/neu
  • IGF1R
  • Muscle neoplasms

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

De Giovanni, C., Landuzzi, L., Palladini, A., Ianzano, M. L., Nicoletti, G., Ruzzi, F., ... Lollini, P. L. (2019). Cancer vaccines co-targeting HER2/NEU and IGF1R. Cancers, 11(4), [517]. https://doi.org/10.3390/cancers11040517

Cancer vaccines co-targeting HER2/NEU and IGF1R. / De Giovanni, Carla; Landuzzi, Lorena; Palladini, Arianna; Ianzano, Marianna Lucia; Nicoletti, Giordano; Ruzzi, Francesca; Amici, Augusto; Croci, Stefania; Nanni, Patrizia; Lollini, Pier Luigi.

In: Cancers, Vol. 11, No. 4, 517, 01.04.2019.

Research output: Contribution to journalArticle

De Giovanni, C, Landuzzi, L, Palladini, A, Ianzano, ML, Nicoletti, G, Ruzzi, F, Amici, A, Croci, S, Nanni, P & Lollini, PL 2019, 'Cancer vaccines co-targeting HER2/NEU and IGF1R', Cancers, vol. 11, no. 4, 517. https://doi.org/10.3390/cancers11040517
De Giovanni C, Landuzzi L, Palladini A, Ianzano ML, Nicoletti G, Ruzzi F et al. Cancer vaccines co-targeting HER2/NEU and IGF1R. Cancers. 2019 Apr 1;11(4). 517. https://doi.org/10.3390/cancers11040517
De Giovanni, Carla ; Landuzzi, Lorena ; Palladini, Arianna ; Ianzano, Marianna Lucia ; Nicoletti, Giordano ; Ruzzi, Francesca ; Amici, Augusto ; Croci, Stefania ; Nanni, Patrizia ; Lollini, Pier Luigi. / Cancer vaccines co-targeting HER2/NEU and IGF1R. In: Cancers. 2019 ; Vol. 11, No. 4.
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abstract = "(1) Background: Human epidermal growth factor receptor 2 (HER2)/neu-driven carcinogenesis is delayed by preventive vaccines able to elicit autochthonous antibodies against HER2/neu. Since cooperation between different receptor tyrosine kinases (RTKs) can occur in human as well as in experimental tumors, we investigated the set-up of DNA and cell vaccines to elicit an antibody response co-targeting two RTKs: HER2/neu and the Insulin-like Growth Factor Receptor-1 (IGF1R). (2) Methods: Plasmid vectors carrying the murine optimized IGF1R sequence or the human IGF1R isoform were used as electroporated DNA vaccines. IGF1R plasmids were transfected in allogeneic HER2/neu-positive IL12-producing murine cancer cells to obtain adjuvanted cell vaccines co-expressing HER2/neu and IGF1R. Vaccination was administered in the preneoplastic stage to mice prone to develop HER2/neu-driven, IGF1R-dependent rhabdomyosarcoma. (3) Results: Electroporated DNA vaccines for murine IGF1R did not elicit anti-mIGF1R antibodies, even when combined with Treg-depletion and/or IL12, while DNA vaccines carrying the human IGF1R elicited antibodies recognizing only the human IGF1R isoform. Cell vaccines co-expressing HER2/neu and murine or human IGF1R succeeded in eliciting antibodies recognizing the murine IGF1R isoform. Cell vaccines co-targeting HER2/neu and murine IGF1R induced the highest level of anti-IGF1R antibodies and nearly significantly delayed the onset of spontaneous rhabdomyosarcomas. (4) Conclusions: Multi-engineered adjuvanted cancer cell vaccines can break the tolerance towards a highly tolerized RTK, such as IGF1R. Cell vaccines co-targeting HER2/neu and IGF1R elicited low levels of specific antibodies that slightly delayed onset of HER2/neu-driven, IGF1R-dependent tumors.",
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AU - Nicoletti, Giordano

AU - Ruzzi, Francesca

AU - Amici, Augusto

AU - Croci, Stefania

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KW - HER2/neu

KW - IGF1R

KW - Muscle neoplasms

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