A GM-CSF and CD40L bystander vaccine is effective in a murine breast cancer model

Hatem Soliman,1 Melanie Mediavilla-Varela,2 Scott J Antonia,3 1Department of Women's Oncology and Experimental Therapeutics, 2Department of Immunology, 3Department of Thoracic Oncology, Moffitt Cancer Center, Tampa, FL, USA Background: There is increasing interest in using cancer vaccines t...

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Autores principales:	Soliman H, Mediavilla-Varela M, Antonia SJ
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2015
Materias:	Breast cancer vaccine immunotherapy cellular therapy Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
Acceso en línea:	https://doaj.org/article/e50d07be5b5e4be5a7ca43898ee64387
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spelling	oai:doaj.org-article:e50d07be5b5e4be5a7ca43898ee643872021-12-02T00:40:53ZA GM-CSF and CD40L bystander vaccine is effective in a murine breast cancer model1179-1314https://doaj.org/article/e50d07be5b5e4be5a7ca43898ee643872015-12-01T00:00:00Zhttps://www.dovepress.com/a-gm-csf-and-cd40l-bystander-vaccine-is-effective-in-a-murine-breast-c-peer-reviewed-article-BCTThttps://doaj.org/toc/1179-1314Hatem Soliman,1 Melanie Mediavilla-Varela,2 Scott J Antonia,3 1Department of Women's Oncology and Experimental Therapeutics, 2Department of Immunology, 3Department of Thoracic Oncology, Moffitt Cancer Center, Tampa, FL, USA Background: There is increasing interest in using cancer vaccines to treat breast cancer patients in the adjuvant setting to prevent recurrence in high risk situations or in combination with other immunomodulators in the advanced setting. Current peptide vaccines are limited by immunologic compatibility issues, and engineered autologous cellular vaccines are difficult to produce on a large scale. Using standardized bystander cell lines modified to secrete immune stimulating adjuvant substances can greatly enhance the ability to produce immunogenic cellular vaccines using unmodified autologous cells or allogeneic medical grade tumor cell lines as targets. We investigated the efficacy of a cellular vaccine using B78H1 bystander cell lines engineered to secrete granulocyte macrophage-colony stimulating factor and CD40 ligand (BCG) in a murine model of breast cancer. Methods: Five-week-old female BALB/c mice were injected orthotopically in the mammary fat pad with 4T1 tumor cells. Treatment consisted of irradiated 4T1 ± BCG cells given subcutaneously every 4 days and was repeated three times per mouse when tumors became palpable. Tumors were measured two to three times per week for 25 days. The vaccine's activity was confirmed in a second experiment using Lewis lung carcinoma (LLC) cells in C57BL/6 mice to exclude a model specific effect. Interferon-γ (IFN-γ) and interleukin-2 (IL-2) enzyme-linked immunospots (ELISPOTS) were performed on splenic lymphocytes incubated with 4T1 lysates along with immunohistochemistry for CD3 on tumor sections. Results: Tumor growth was significantly inhibited in the 4T1-BCG and LLC-BCG treatment groups when compared to 4T1 and LLC treatment groups. There were higher levels of IL-2 and IFN-γ secreting T-cells on ELISPOT for BCG treated groups, and a trend for higher numbers of tumor infiltrating CD3+ lymphocytes. Some tumors in the 4T1-BCG demonstrated organized lymphoid structures within the tumor microenvironment as well. Conclusion: The use of BCG bystander cell lines demonstrates proof of concept for anti-tumor activity and immunogenicity in an immunocompetent murine model of breast cancer. This vaccine is being evaluated in lung cancer and should be explored further in clinical trials of breast cancer patients at high risk of recurrence or in combination with other immunomodulatory agents. Keywords: breast cancer, immunotherapy, bystander vaccine, CD40L, GM-CSFSoliman HMediavilla-Varela MAntonia SJDove Medical PressarticleBreast cancervaccineimmunotherapycellular therapyNeoplasms. Tumors. Oncology. Including cancer and carcinogensRC254-282ENBreast Cancer: Targets and Therapy, Vol 2015, Iss Issue 1, Pp 389-397 (2015)
institution	DOAJ
collection	DOAJ
language	EN
topic	Breast cancer vaccine immunotherapy cellular therapy Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
spellingShingle	Breast cancer vaccine immunotherapy cellular therapy Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282 Soliman H Mediavilla-Varela M Antonia SJ A GM-CSF and CD40L bystander vaccine is effective in a murine breast cancer model
description	Hatem Soliman,1 Melanie Mediavilla-Varela,2 Scott J Antonia,3 1Department of Women's Oncology and Experimental Therapeutics, 2Department of Immunology, 3Department of Thoracic Oncology, Moffitt Cancer Center, Tampa, FL, USA Background: There is increasing interest in using cancer vaccines to treat breast cancer patients in the adjuvant setting to prevent recurrence in high risk situations or in combination with other immunomodulators in the advanced setting. Current peptide vaccines are limited by immunologic compatibility issues, and engineered autologous cellular vaccines are difficult to produce on a large scale. Using standardized bystander cell lines modified to secrete immune stimulating adjuvant substances can greatly enhance the ability to produce immunogenic cellular vaccines using unmodified autologous cells or allogeneic medical grade tumor cell lines as targets. We investigated the efficacy of a cellular vaccine using B78H1 bystander cell lines engineered to secrete granulocyte macrophage-colony stimulating factor and CD40 ligand (BCG) in a murine model of breast cancer. Methods: Five-week-old female BALB/c mice were injected orthotopically in the mammary fat pad with 4T1 tumor cells. Treatment consisted of irradiated 4T1 ± BCG cells given subcutaneously every 4 days and was repeated three times per mouse when tumors became palpable. Tumors were measured two to three times per week for 25 days. The vaccine's activity was confirmed in a second experiment using Lewis lung carcinoma (LLC) cells in C57BL/6 mice to exclude a model specific effect. Interferon-γ (IFN-γ) and interleukin-2 (IL-2) enzyme-linked immunospots (ELISPOTS) were performed on splenic lymphocytes incubated with 4T1 lysates along with immunohistochemistry for CD3 on tumor sections. Results: Tumor growth was significantly inhibited in the 4T1-BCG and LLC-BCG treatment groups when compared to 4T1 and LLC treatment groups. There were higher levels of IL-2 and IFN-γ secreting T-cells on ELISPOT for BCG treated groups, and a trend for higher numbers of tumor infiltrating CD3+ lymphocytes. Some tumors in the 4T1-BCG demonstrated organized lymphoid structures within the tumor microenvironment as well. Conclusion: The use of BCG bystander cell lines demonstrates proof of concept for anti-tumor activity and immunogenicity in an immunocompetent murine model of breast cancer. This vaccine is being evaluated in lung cancer and should be explored further in clinical trials of breast cancer patients at high risk of recurrence or in combination with other immunomodulatory agents. Keywords: breast cancer, immunotherapy, bystander vaccine, CD40L, GM-CSF
format	article
author	Soliman H Mediavilla-Varela M Antonia SJ
author_facet	Soliman H Mediavilla-Varela M Antonia SJ
author_sort	Soliman H
title	A GM-CSF and CD40L bystander vaccine is effective in a murine breast cancer model
title_short	A GM-CSF and CD40L bystander vaccine is effective in a murine breast cancer model
title_full	A GM-CSF and CD40L bystander vaccine is effective in a murine breast cancer model
title_fullStr	A GM-CSF and CD40L bystander vaccine is effective in a murine breast cancer model
title_full_unstemmed	A GM-CSF and CD40L bystander vaccine is effective in a murine breast cancer model
title_sort	gm-csf and cd40l bystander vaccine is effective in a murine breast cancer model
publisher	Dove Medical Press
publishDate	2015
url	https://doaj.org/article/e50d07be5b5e4be5a7ca43898ee64387
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A GM-CSF and CD40L bystander vaccine is effective in a murine breast cancer model

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