Oncolytic adenoviruses coated with MHC-I tumor epitopes increase the anti-tumor immunity and efficacy against melanoma

Cristian Capasso, Mari Hirvinen, Mariangela Garofalo, Dmitrii Romaniuk, Lukasz Kuryk, Teea Sarvela, Andrea Vitale, Maxim Antopolsky, Aniket Magarkar, Tapani Viitala, Teemu Suutari, Alex Bunker, Marjo Yliperttula, Arto Urtti, Vincenzo Cerullo

Research output: Contribution to journalArticleScientificpeer-review

Abstract

The stimulation of the immune system using oncolytic adenoviruses (OAds) has attracted significant interest and several studies suggested that OAd´s immunogenicity might be important for their efficacy. Therefore, we developed a versatile and rapid system to adsorb tumor-specific major histocompatibility complex class I (MHC-I) peptides onto the viral surface to drive the immune response towards the tumor-epitopes. By studying the model epitope SIINFEKL we demonstrated that the peptide-coated OAd (PeptiCRAd) retains its infectivity and the cross-presentation of the modified-exogenous epitope on MHC-I is not hindered. We then showed that the SIINFEKL-targeting PeptiCRAd achieves a superior anti-tumor efficacy and increases the percentage of anti-tumor CD8+ T-cells and mature epitope-specific dendritic cells in vivo. PeptiCRAds loaded with clinically relevant tumor epitopes derived from tyrosinase-related protein 2 (TRP-2) and human gp100 could reduce the growth of primary-treated tumors and secondary-untreated melanomas, promoting the expansion of antigen-specific T-cell populations. Finally, we tested PeptiCRAd in humanized mice bearing human melanomas. In this model, a PeptiCRAd targeting the human melanoma-associated antigen A1 (MAGE-A1) and expressing granulocyte and macrophage colony-stimulating factor (GM-CSF) was able to eradicate established tumors and increased the human MAGE-A1-specific CD8+ T-cell population. Herein we show that the immunogenicity of OAds plays a key role in their efficacy and it can be exploited to direct the immune response system towards exogenous tumor epitopes. This versatile and rapid system overcomes the immunodominance of the virus and elicits a tumor-specific immune response, making PeptiCRAd a promising approach for clinical testing.
Original languageEnglish
Article number1105429
JournalOncoImmunology
Volume5
Issue number4
Number of pages11
ISSN2162-402X
DOIs
Publication statusPublished - 2016
MoE publication typeA1 Journal article-refereed

Fields of Science

  • 1182 Biochemistry, cell and molecular biology
  • Oncolytic adenovirus
  • cancer vaccines
  • Immunotherapy
  • Melanoma
  • humanized mice

Cite this

Capasso, Cristian ; Hirvinen, Mari ; Garofalo, Mariangela ; Romaniuk, Dmitrii ; Kuryk, Lukasz ; Sarvela, Teea ; Vitale, Andrea ; Antopolsky, Maxim ; Magarkar, Aniket ; Viitala, Tapani ; Suutari, Teemu ; Bunker, Alex ; Yliperttula, Marjo ; Urtti, Arto ; Cerullo, Vincenzo. / Oncolytic adenoviruses coated with MHC-I tumor epitopes increase the anti-tumor immunity and efficacy against melanoma. In: OncoImmunology. 2016 ; Vol. 5, No. 4.
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abstract = "The stimulation of the immune system using oncolytic adenoviruses (OAds) has attracted significant interest and several studies suggested that OAd´s immunogenicity might be important for their efficacy. Therefore, we developed a versatile and rapid system to adsorb tumor-specific major histocompatibility complex class I (MHC-I) peptides onto the viral surface to drive the immune response towards the tumor-epitopes. By studying the model epitope SIINFEKL we demonstrated that the peptide-coated OAd (PeptiCRAd) retains its infectivity and the cross-presentation of the modified-exogenous epitope on MHC-I is not hindered. We then showed that the SIINFEKL-targeting PeptiCRAd achieves a superior anti-tumor efficacy and increases the percentage of anti-tumor CD8+ T-cells and mature epitope-specific dendritic cells in vivo. PeptiCRAds loaded with clinically relevant tumor epitopes derived from tyrosinase-related protein 2 (TRP-2) and human gp100 could reduce the growth of primary-treated tumors and secondary-untreated melanomas, promoting the expansion of antigen-specific T-cell populations. Finally, we tested PeptiCRAd in humanized mice bearing human melanomas. In this model, a PeptiCRAd targeting the human melanoma-associated antigen A1 (MAGE-A1) and expressing granulocyte and macrophage colony-stimulating factor (GM-CSF) was able to eradicate established tumors and increased the human MAGE-A1-specific CD8+ T-cell population. Herein we show that the immunogenicity of OAds plays a key role in their efficacy and it can be exploited to direct the immune response system towards exogenous tumor epitopes. This versatile and rapid system overcomes the immunodominance of the virus and elicits a tumor-specific immune response, making PeptiCRAd a promising approach for clinical testing.",
keywords = "1182 Biochemistry, cell and molecular biology, Oncolytic adenovirus, cancer vaccines, Immunotherapy, Melanoma, humanized mice",
author = "Cristian Capasso and Mari Hirvinen and Mariangela Garofalo and Dmitrii Romaniuk and Lukasz Kuryk and Teea Sarvela and Andrea Vitale and Maxim Antopolsky and Aniket Magarkar and Tapani Viitala and Teemu Suutari and Alex Bunker and Marjo Yliperttula and Arto Urtti and Vincenzo Cerullo",
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Oncolytic adenoviruses coated with MHC-I tumor epitopes increase the anti-tumor immunity and efficacy against melanoma. / Capasso, Cristian; Hirvinen, Mari ; Garofalo, Mariangela; Romaniuk, Dmitrii; Kuryk, Lukasz; Sarvela, Teea; Vitale, Andrea; Antopolsky, Maxim; Magarkar, Aniket; Viitala, Tapani ; Suutari, Teemu ; Bunker, Alex; Yliperttula, Marjo ; Urtti, Arto ; Cerullo, Vincenzo.

In: OncoImmunology, Vol. 5, No. 4, 1105429, 2016.

Research output: Contribution to journalArticleScientificpeer-review

TY - JOUR

T1 - Oncolytic adenoviruses coated with MHC-I tumor epitopes increase the anti-tumor immunity and efficacy against melanoma

AU - Capasso, Cristian

AU - Hirvinen, Mari

AU - Garofalo, Mariangela

AU - Romaniuk, Dmitrii

AU - Kuryk, Lukasz

AU - Sarvela, Teea

AU - Vitale, Andrea

AU - Antopolsky, Maxim

AU - Magarkar, Aniket

AU - Viitala, Tapani

AU - Suutari, Teemu

AU - Bunker, Alex

AU - Yliperttula, Marjo

AU - Urtti, Arto

AU - Cerullo, Vincenzo

PY - 2016

Y1 - 2016

N2 - The stimulation of the immune system using oncolytic adenoviruses (OAds) has attracted significant interest and several studies suggested that OAd´s immunogenicity might be important for their efficacy. Therefore, we developed a versatile and rapid system to adsorb tumor-specific major histocompatibility complex class I (MHC-I) peptides onto the viral surface to drive the immune response towards the tumor-epitopes. By studying the model epitope SIINFEKL we demonstrated that the peptide-coated OAd (PeptiCRAd) retains its infectivity and the cross-presentation of the modified-exogenous epitope on MHC-I is not hindered. We then showed that the SIINFEKL-targeting PeptiCRAd achieves a superior anti-tumor efficacy and increases the percentage of anti-tumor CD8+ T-cells and mature epitope-specific dendritic cells in vivo. PeptiCRAds loaded with clinically relevant tumor epitopes derived from tyrosinase-related protein 2 (TRP-2) and human gp100 could reduce the growth of primary-treated tumors and secondary-untreated melanomas, promoting the expansion of antigen-specific T-cell populations. Finally, we tested PeptiCRAd in humanized mice bearing human melanomas. In this model, a PeptiCRAd targeting the human melanoma-associated antigen A1 (MAGE-A1) and expressing granulocyte and macrophage colony-stimulating factor (GM-CSF) was able to eradicate established tumors and increased the human MAGE-A1-specific CD8+ T-cell population. Herein we show that the immunogenicity of OAds plays a key role in their efficacy and it can be exploited to direct the immune response system towards exogenous tumor epitopes. This versatile and rapid system overcomes the immunodominance of the virus and elicits a tumor-specific immune response, making PeptiCRAd a promising approach for clinical testing.

AB - The stimulation of the immune system using oncolytic adenoviruses (OAds) has attracted significant interest and several studies suggested that OAd´s immunogenicity might be important for their efficacy. Therefore, we developed a versatile and rapid system to adsorb tumor-specific major histocompatibility complex class I (MHC-I) peptides onto the viral surface to drive the immune response towards the tumor-epitopes. By studying the model epitope SIINFEKL we demonstrated that the peptide-coated OAd (PeptiCRAd) retains its infectivity and the cross-presentation of the modified-exogenous epitope on MHC-I is not hindered. We then showed that the SIINFEKL-targeting PeptiCRAd achieves a superior anti-tumor efficacy and increases the percentage of anti-tumor CD8+ T-cells and mature epitope-specific dendritic cells in vivo. PeptiCRAds loaded with clinically relevant tumor epitopes derived from tyrosinase-related protein 2 (TRP-2) and human gp100 could reduce the growth of primary-treated tumors and secondary-untreated melanomas, promoting the expansion of antigen-specific T-cell populations. Finally, we tested PeptiCRAd in humanized mice bearing human melanomas. In this model, a PeptiCRAd targeting the human melanoma-associated antigen A1 (MAGE-A1) and expressing granulocyte and macrophage colony-stimulating factor (GM-CSF) was able to eradicate established tumors and increased the human MAGE-A1-specific CD8+ T-cell population. Herein we show that the immunogenicity of OAds plays a key role in their efficacy and it can be exploited to direct the immune response system towards exogenous tumor epitopes. This versatile and rapid system overcomes the immunodominance of the virus and elicits a tumor-specific immune response, making PeptiCRAd a promising approach for clinical testing.

KW - 1182 Biochemistry, cell and molecular biology

KW - Oncolytic adenovirus

KW - cancer vaccines

KW - Immunotherapy

KW - Melanoma

KW - humanized mice

U2 - 10.1080/2162402X.2015.1105429

DO - 10.1080/2162402X.2015.1105429

M3 - Article

VL - 5

JO - OncoImmunology

JF - OncoImmunology

SN - 2162-4011

IS - 4

M1 - 1105429

ER -