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

Abstract

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). 

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. 

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. 

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
Pages (from-to)1-12
Number of pages12
JournalCancers
Volume11
Issue number4
DOIs
Publication statusPublished - Apr 11 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

  • DNA vaccines
  • HER2/neu
  • IGF1R
  • cancer vaccines
  • muscle neoplasms

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), 1-12. 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, 11.04.2019, p. 1-12.

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, P-L 2019, 'Cancer Vaccines Co-Targeting HER2/Neu and IGF1R', Cancers, vol. 11, no. 4, pp. 1-12. 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 11;11(4):1-12. 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. pp. 1-12.
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abstract = "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). 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. 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. 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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T1 - Cancer Vaccines Co-Targeting HER2/Neu and IGF1R

AU - De Giovanni, Carla

AU - Landuzzi, Lorena

AU - Palladini, Arianna

AU - Ianzano, Marianna Lucia

AU - Nicoletti, Giordano

AU - Ruzzi, Francesca

AU - Amici, Augusto

AU - Croci, Stefania

AU - Nanni, Patrizia

AU - Lollini, Pier-Luigi

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N2 - 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). 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. 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. 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.

AB - 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). 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. 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. 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.

KW - DNA vaccines

KW - HER2/neu

KW - IGF1R

KW - cancer vaccines

KW - muscle neoplasms

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JO - Cancers

JF - Cancers

SN - 2072-6694

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