Comparative analysis of cancer vaccine settings for the selection of an effective protocol in mice

Francesca Kalli, Rodolfo Machiorlatti, Florinda Battaglia, Alessia Parodi, Giuseppina Conteduca, Francesca Ferrera, Michele Proietti, Samuele Tardito, Marina Sanguineti, Enrico Millo, Daniela Fenoglio, Raffaele De Palma, Giorgio Inghirami, Gilberto Filaci

Research output: Contribution to journalArticle

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Abstract

Background: Cancer vaccines are considered a promising therapeutic approach. However, their clinical results are not yet satisfactory. This may be due to the the difficulty of selection of an efficient tumor associated antigen (TAA) and immunization protocol. Indeed, the weak antigenicity of many TAA impairs the design of robust procedures, therefore a systematic analysis to identify the most efficient TAA is mandatory. Here, we performed a study to compare different gp100 vaccination strategies to identify the best strategy to provide a 100% protection against experimental melanoma in a reproducible manner.Methods: C57BL/6J mice were challenged subcutaneously with B16F10 melanoma cells, after vaccination with: a) mouse or human gp10025-33 peptide plus CpG adjuvant; b) mouse or human gp100 gene; c) mouse or human gp10025-33 peptide-pulsed dendritic cells (DC). Alternatively, a neutralizing anti-IL-10 monoclonal antibody (mAb) was subcutaneously administered at the site of tumor challenge to counteract regulatory cells. Finally, combinatorial treatment was performed associating human gp10025-33 peptide-pulsed DC vaccination with administration of the anti-IL-10 mAb.Results: Vaccination with human gp10025-33 peptide-pulsed DC was the most effective immunization protocol, although not achieving a full protection. Administration of the anti-IL-10 mAb showed also a remarkable protective effect, replicated in mice challenged with a different tumor, Anaplastic Large Cell Lymphoma. When immunization with gp10025-33 peptide-pulsed DC was associated with IL-10 counteraction, a 100% protective effect was consistently achieved. The analysis on the T-cell tumor infiltrates showed an increase of CD4+granzyme+ T-cells and a decreased number of CD4+CD25+Foxp3+ Treg elements from mice treated with either gp10025-33 peptide-pulsed DC vaccination or anti-IL-10 mAb administration. These data suggest that processes of intratumoral re-balance between effector and regulatory T cell subpopulations may play a critical protective role in immunotherapy protocols.Conclusions: Here we demonstrate that, in the setting of a cancer vaccine strategy, a comparative analysis of different personalized approaches may favour the unveiling of the most effective protocol. Moreover, our findings suggest that counteraction of IL-10 activity may be critical to revert the intratumoral environment promoting Treg polarization, thus increasing the effects of a vaccination against selected TAA.

Original languageEnglish
Article number120
JournalJournal of Translational Medicine
Volume11
Issue number1
DOIs
Publication statusPublished - May 12 2013

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Cancer Vaccines
Interleukin-10
Tumors
Vaccination
Dendritic Cells
Neoplasm Antigens
Peptides
Immunization
T-cells
Monoclonal Antibodies
Antigens
Anaplastic Large-Cell Lymphoma
T-Lymphocytes
Granzymes
Neoplasms
Experimental Melanomas
Regulatory T-Lymphocytes
Inbred C57BL Mouse
Immunotherapy
Melanoma

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Comparative analysis of cancer vaccine settings for the selection of an effective protocol in mice. / Kalli, Francesca; Machiorlatti, Rodolfo; Battaglia, Florinda; Parodi, Alessia; Conteduca, Giuseppina; Ferrera, Francesca; Proietti, Michele; Tardito, Samuele; Sanguineti, Marina; Millo, Enrico; Fenoglio, Daniela; De Palma, Raffaele; Inghirami, Giorgio; Filaci, Gilberto.

In: Journal of Translational Medicine, Vol. 11, No. 1, 120, 12.05.2013.

Research output: Contribution to journalArticle

Kalli, F, Machiorlatti, R, Battaglia, F, Parodi, A, Conteduca, G, Ferrera, F, Proietti, M, Tardito, S, Sanguineti, M, Millo, E, Fenoglio, D, De Palma, R, Inghirami, G & Filaci, G 2013, 'Comparative analysis of cancer vaccine settings for the selection of an effective protocol in mice', Journal of Translational Medicine, vol. 11, no. 1, 120. https://doi.org/10.1186/1479-5876-11-120
Kalli, Francesca ; Machiorlatti, Rodolfo ; Battaglia, Florinda ; Parodi, Alessia ; Conteduca, Giuseppina ; Ferrera, Francesca ; Proietti, Michele ; Tardito, Samuele ; Sanguineti, Marina ; Millo, Enrico ; Fenoglio, Daniela ; De Palma, Raffaele ; Inghirami, Giorgio ; Filaci, Gilberto. / Comparative analysis of cancer vaccine settings for the selection of an effective protocol in mice. In: Journal of Translational Medicine. 2013 ; Vol. 11, No. 1.
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AU - Kalli, Francesca

AU - Machiorlatti, Rodolfo

AU - Battaglia, Florinda

AU - Parodi, Alessia

AU - Conteduca, Giuseppina

AU - Ferrera, Francesca

AU - Proietti, Michele

AU - Tardito, Samuele

AU - Sanguineti, Marina

AU - Millo, Enrico

AU - Fenoglio, Daniela

AU - De Palma, Raffaele

AU - Inghirami, Giorgio

AU - Filaci, Gilberto

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N2 - Background: Cancer vaccines are considered a promising therapeutic approach. However, their clinical results are not yet satisfactory. This may be due to the the difficulty of selection of an efficient tumor associated antigen (TAA) and immunization protocol. Indeed, the weak antigenicity of many TAA impairs the design of robust procedures, therefore a systematic analysis to identify the most efficient TAA is mandatory. Here, we performed a study to compare different gp100 vaccination strategies to identify the best strategy to provide a 100% protection against experimental melanoma in a reproducible manner.Methods: C57BL/6J mice were challenged subcutaneously with B16F10 melanoma cells, after vaccination with: a) mouse or human gp10025-33 peptide plus CpG adjuvant; b) mouse or human gp100 gene; c) mouse or human gp10025-33 peptide-pulsed dendritic cells (DC). Alternatively, a neutralizing anti-IL-10 monoclonal antibody (mAb) was subcutaneously administered at the site of tumor challenge to counteract regulatory cells. Finally, combinatorial treatment was performed associating human gp10025-33 peptide-pulsed DC vaccination with administration of the anti-IL-10 mAb.Results: Vaccination with human gp10025-33 peptide-pulsed DC was the most effective immunization protocol, although not achieving a full protection. Administration of the anti-IL-10 mAb showed also a remarkable protective effect, replicated in mice challenged with a different tumor, Anaplastic Large Cell Lymphoma. When immunization with gp10025-33 peptide-pulsed DC was associated with IL-10 counteraction, a 100% protective effect was consistently achieved. The analysis on the T-cell tumor infiltrates showed an increase of CD4+granzyme+ T-cells and a decreased number of CD4+CD25+Foxp3+ Treg elements from mice treated with either gp10025-33 peptide-pulsed DC vaccination or anti-IL-10 mAb administration. These data suggest that processes of intratumoral re-balance between effector and regulatory T cell subpopulations may play a critical protective role in immunotherapy protocols.Conclusions: Here we demonstrate that, in the setting of a cancer vaccine strategy, a comparative analysis of different personalized approaches may favour the unveiling of the most effective protocol. Moreover, our findings suggest that counteraction of IL-10 activity may be critical to revert the intratumoral environment promoting Treg polarization, thus increasing the effects of a vaccination against selected TAA.

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