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Systemic Delivery of Oncolytic Adenovirus to Tumors Using Tumor-Infiltrating Lymphocytes as Carriers

Immunotherapy with tumor-infiltrating lymphocytes (TIL) or oncolytic adenoviruses, have shown promising results in cancer treatment, when used as separate therapies. When used in combination, the antitumor effect is synergistically potentiated due oncolytic adenovirus infection and its immune stimul...

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Autores principales: Santos, Joao, Heiniö, Camilla, Quixabeira, Dafne, Zafar, Sadia, Clubb, James, Pakola, Santeri, Cervera-Carrascon, Victor, Havunen, Riikka, Kanerva, Anna, Hemminki, Akseli
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8143525/
https://www.ncbi.nlm.nih.gov/pubmed/33922052
http://dx.doi.org/10.3390/cells10050978
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author Santos, Joao
Heiniö, Camilla
Quixabeira, Dafne
Zafar, Sadia
Clubb, James
Pakola, Santeri
Cervera-Carrascon, Victor
Havunen, Riikka
Kanerva, Anna
Hemminki, Akseli
author_facet Santos, Joao
Heiniö, Camilla
Quixabeira, Dafne
Zafar, Sadia
Clubb, James
Pakola, Santeri
Cervera-Carrascon, Victor
Havunen, Riikka
Kanerva, Anna
Hemminki, Akseli
author_sort Santos, Joao
collection PubMed
description Immunotherapy with tumor-infiltrating lymphocytes (TIL) or oncolytic adenoviruses, have shown promising results in cancer treatment, when used as separate therapies. When used in combination, the antitumor effect is synergistically potentiated due oncolytic adenovirus infection and its immune stimulating effects on T cells. Indeed, studies in hamsters have shown a 100% complete response rate when animals were treated with oncolytic adenovirus coding for TNFa and IL-2 (Ad5/3-E2F-D24-hTNFa-IRES-hIL2; TILT-123) and TIL therapy. In humans, one caveat with oncolytic virus therapy is that intratumoral injection has been traditionally preferred over systemic administration, for achieving sufficient virus concentrations in tumors, especially when neutralizing antibodies emerge. We have previously shown that 5/3 chimeric oncolytic adenovirus can bind to human lymphocytes for avoidance of neutralization. In this study, we hypothesized that incubation of oncolytic adenovirus (TILT-123) with TILs prior to systemic injection would allow delivery of virus to tumors. This approach would deliver both components in one self-amplifying product. TILs would help deliver TILT-123, whose replication will recruit more TILs and increase their cytotoxicity. In vitro, TILT-123 was seen binding efficiently to lymphocytes, supporting the idea of dual administration. We show in vivo in different models that virus could be delivered to tumors with TILs as carriers.
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spelling pubmed-81435252021-05-25 Systemic Delivery of Oncolytic Adenovirus to Tumors Using Tumor-Infiltrating Lymphocytes as Carriers Santos, Joao Heiniö, Camilla Quixabeira, Dafne Zafar, Sadia Clubb, James Pakola, Santeri Cervera-Carrascon, Victor Havunen, Riikka Kanerva, Anna Hemminki, Akseli Cells Article Immunotherapy with tumor-infiltrating lymphocytes (TIL) or oncolytic adenoviruses, have shown promising results in cancer treatment, when used as separate therapies. When used in combination, the antitumor effect is synergistically potentiated due oncolytic adenovirus infection and its immune stimulating effects on T cells. Indeed, studies in hamsters have shown a 100% complete response rate when animals were treated with oncolytic adenovirus coding for TNFa and IL-2 (Ad5/3-E2F-D24-hTNFa-IRES-hIL2; TILT-123) and TIL therapy. In humans, one caveat with oncolytic virus therapy is that intratumoral injection has been traditionally preferred over systemic administration, for achieving sufficient virus concentrations in tumors, especially when neutralizing antibodies emerge. We have previously shown that 5/3 chimeric oncolytic adenovirus can bind to human lymphocytes for avoidance of neutralization. In this study, we hypothesized that incubation of oncolytic adenovirus (TILT-123) with TILs prior to systemic injection would allow delivery of virus to tumors. This approach would deliver both components in one self-amplifying product. TILs would help deliver TILT-123, whose replication will recruit more TILs and increase their cytotoxicity. In vitro, TILT-123 was seen binding efficiently to lymphocytes, supporting the idea of dual administration. We show in vivo in different models that virus could be delivered to tumors with TILs as carriers. MDPI 2021-04-22 /pmc/articles/PMC8143525/ /pubmed/33922052 http://dx.doi.org/10.3390/cells10050978 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Santos, Joao
Heiniö, Camilla
Quixabeira, Dafne
Zafar, Sadia
Clubb, James
Pakola, Santeri
Cervera-Carrascon, Victor
Havunen, Riikka
Kanerva, Anna
Hemminki, Akseli
Systemic Delivery of Oncolytic Adenovirus to Tumors Using Tumor-Infiltrating Lymphocytes as Carriers
title Systemic Delivery of Oncolytic Adenovirus to Tumors Using Tumor-Infiltrating Lymphocytes as Carriers
title_full Systemic Delivery of Oncolytic Adenovirus to Tumors Using Tumor-Infiltrating Lymphocytes as Carriers
title_fullStr Systemic Delivery of Oncolytic Adenovirus to Tumors Using Tumor-Infiltrating Lymphocytes as Carriers
title_full_unstemmed Systemic Delivery of Oncolytic Adenovirus to Tumors Using Tumor-Infiltrating Lymphocytes as Carriers
title_short Systemic Delivery of Oncolytic Adenovirus to Tumors Using Tumor-Infiltrating Lymphocytes as Carriers
title_sort systemic delivery of oncolytic adenovirus to tumors using tumor-infiltrating lymphocytes as carriers
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8143525/
https://www.ncbi.nlm.nih.gov/pubmed/33922052
http://dx.doi.org/10.3390/cells10050978
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