1100 Immunovirotherapy with the codon-modified influenza virus CodaLytic™ modulates the quality of the tumor immune infiltrate in support of anti-tumor immunity

BackgroundVirotherapeutics leverage oncolytic and pro-inflammatory properties to ultimately engage multiple mechanisms of action that lead to holistic modulation of the tumor microenvironment (TME) and induction of anti-tumor immunity. As such, they serve as off-the-shelf in situ cancer vaccines to...

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Published in:Journal for immunotherapy of cancer 2023-11, Vol.11 (Suppl 1), p.A1211-A1211
Main Authors: Zhao, Yiwen, Jahan, Nusrat, Blagovic, Katarina, Mueller, Steffen, Robert Coleman, J, Kaufmann, Johanna K
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Breast cancer
Immunity (Disease)
Immunotherapy
Influenza
Lymphocytes
Regular and Young Investigator Award Abstracts
Tumors
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container_issue Suppl 1
container_start_page A1211
container_title Journal for immunotherapy of cancer
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creator Zhao, Yiwen
Jahan, Nusrat
Blagovic, Katarina
Mueller, Steffen
Robert Coleman, J
Kaufmann, Johanna K
description BackgroundVirotherapeutics leverage oncolytic and pro-inflammatory properties to ultimately engage multiple mechanisms of action that lead to holistic modulation of the tumor microenvironment (TME) and induction of anti-tumor immunity. As such, they serve as off-the-shelf in situ cancer vaccines to generate a personalized immune response. We have previously introduced CodaLytic, a codon-modified influenza virus, as an efficient kick-starter of the cancer immunity cycle in several murine models with different baseline immune contexture and in human tumor explant cultures. Here, we are presenting a deeper dive into the immune cell composition infiltrating syngeneic mouse tumors after treatment with CodaLytic.MethodsEffects on the TME were measured after intratumoral administration of 108 PFU CodaLytic as monotherapy and in combination with immune checkpoint blockade (ICB) and/or chemotherapy in orthotopic EMT6 and 4T1 triple-negative breast cancer, subcutaneous B16-F10 melanoma and MC38 colon cancer mouse models. Tumors were harvested and dissociated for characterization of immune infiltrate by flow cytometry after ≥2 doses of virus and after onset of efficacy based on tumor volume in at least one experimental group.ResultsAcross all models, virus treatment increased tumor infiltration with T and antigen-presenting cells, which could be further boosted by addition of ICB. Both total CD3+ T and importantly CD8+ T cells were recruited to tumors in response to treatment and their frequency within the immune infiltrate correlated directly with tumor volumes (CD3+: MC38 R2=0.58, p
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As such, they serve as off-the-shelf in situ cancer vaccines to generate a personalized immune response. We have previously introduced CodaLytic, a codon-modified influenza virus, as an efficient kick-starter of the cancer immunity cycle in several murine models with different baseline immune contexture and in human tumor explant cultures. Here, we are presenting a deeper dive into the immune cell composition infiltrating syngeneic mouse tumors after treatment with CodaLytic.MethodsEffects on the TME were measured after intratumoral administration of 108 PFU CodaLytic as monotherapy and in combination with immune checkpoint blockade (ICB) and/or chemotherapy in orthotopic EMT6 and 4T1 triple-negative breast cancer, subcutaneous B16-F10 melanoma and MC38 colon cancer mouse models. Tumors were harvested and dissociated for characterization of immune infiltrate by flow cytometry after ≥2 doses of virus and after onset of efficacy based on tumor volume in at least one experimental group.ResultsAcross all models, virus treatment increased tumor infiltration with T and antigen-presenting cells, which could be further boosted by addition of ICB. Both total CD3+ T and importantly CD8+ T cells were recruited to tumors in response to treatment and their frequency within the immune infiltrate correlated directly with tumor volumes (CD3+: MC38 R2=0.58, p<0.02; EMT6 R2=0.31, p<0.02; 4T1 R2=0.50, p<0.0001. CD8+: MC38 R2=0.60, p<0.02; EMT6 R2=0.20, p<0.05; 4T1 R2=0.15, p<0.05). Interestingly, addition of ICB further supported the increase of T cell infiltration in alignment with improved efficacy, while Granzyme B expression was primarily driven by CodaLytic, in particular in B16 and MC38 models, independently of combination with PD-1 blockade. Importantly, these increases were not offset by parallel recruitment of regulatory T cells in B16 and EMT6 models. Furthermore, the frequency of the cross-presenting subset of dendritic cells increased after CodaLytic treatment and directly associated with tumor volume (4T1: R2=0.30, p<0.01). A TME conducive to anti-tumor immunity was further supported by recruitment of B, NK and CD4+ T cells.ConclusionsCodaLytic treatment induced changes in the murine tumor immune infiltrate suggesting anti-tumor immune activity independently of the baseline immune contexture associated with the tumor model. This supports the utility of CodaLytic, a codon-modified virus being developed for breast cancer immunovirotherapy, as a valuable component of novel therapeutic regimens.Ethics ApprovalThe animal work in this study was approved after MisPro Biotech Services IACUC review, protocols 2019–01-17-COD-1, 2022-COD-02 and LC 2022-COD-03. MC38 data was generated according to the IACUC guidelines of Champions Oncology.]]></description><identifier>EISSN: 2051-1426</identifier><identifier>DOI: 10.1136/jitc-2023-SITC2023.1100</identifier><language>eng</language><publisher>London: BMJ Publishing Group Ltd</publisher><subject>Breast cancer ; Immunity (Disease) ; Immunotherapy ; Influenza ; Lymphocytes ; Regular and Young Investigator Award Abstracts ; Tumors</subject><ispartof>Journal for immunotherapy of cancer, 2023-11, Vol.11 (Suppl 1), p.A1211-A1211</ispartof><rights>Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.</rights><rights>2023 Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ. http://creativecommons.org/licenses/by-nc/4.0/ This is an open access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited, appropriate credit is given, any changes made indicated, and the use is non-commercial. See http://creativecommons.org/licenses/by-nc/4.0/ . Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://jitc.bmj.com/content/11/Suppl_1/A1211.full.pdf$$EPDF$$P50$$Gbmj$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://jitc.bmj.com/content/11/Suppl_1/A1211.full$$EHTML$$P50$$Gbmj$$Hfree_for_read</linktohtml><link.rule.ids>314,780,784,27924,27925,37012,55350,77660,77686</link.rule.ids></links><search><creatorcontrib>Zhao, Yiwen</creatorcontrib><creatorcontrib>Jahan, Nusrat</creatorcontrib><creatorcontrib>Blagovic, Katarina</creatorcontrib><creatorcontrib>Mueller, Steffen</creatorcontrib><creatorcontrib>Robert Coleman, J</creatorcontrib><creatorcontrib>Kaufmann, Johanna K</creatorcontrib><title>1100 Immunovirotherapy with the codon-modified influenza virus CodaLytic™ modulates the quality of the tumor immune infiltrate in support of anti-tumor immunity</title><title>Journal for immunotherapy of cancer</title><addtitle>J Immunother Cancer</addtitle><description><![CDATA[BackgroundVirotherapeutics leverage oncolytic and pro-inflammatory properties to ultimately engage multiple mechanisms of action that lead to holistic modulation of the tumor microenvironment (TME) and induction of anti-tumor immunity. As such, they serve as off-the-shelf in situ cancer vaccines to generate a personalized immune response. We have previously introduced CodaLytic, a codon-modified influenza virus, as an efficient kick-starter of the cancer immunity cycle in several murine models with different baseline immune contexture and in human tumor explant cultures. Here, we are presenting a deeper dive into the immune cell composition infiltrating syngeneic mouse tumors after treatment with CodaLytic.MethodsEffects on the TME were measured after intratumoral administration of 108 PFU CodaLytic as monotherapy and in combination with immune checkpoint blockade (ICB) and/or chemotherapy in orthotopic EMT6 and 4T1 triple-negative breast cancer, subcutaneous B16-F10 melanoma and MC38 colon cancer mouse models. Tumors were harvested and dissociated for characterization of immune infiltrate by flow cytometry after ≥2 doses of virus and after onset of efficacy based on tumor volume in at least one experimental group.ResultsAcross all models, virus treatment increased tumor infiltration with T and antigen-presenting cells, which could be further boosted by addition of ICB. Both total CD3+ T and importantly CD8+ T cells were recruited to tumors in response to treatment and their frequency within the immune infiltrate correlated directly with tumor volumes (CD3+: MC38 R2=0.58, p<0.02; EMT6 R2=0.31, p<0.02; 4T1 R2=0.50, p<0.0001. CD8+: MC38 R2=0.60, p<0.02; EMT6 R2=0.20, p<0.05; 4T1 R2=0.15, p<0.05). Interestingly, addition of ICB further supported the increase of T cell infiltration in alignment with improved efficacy, while Granzyme B expression was primarily driven by CodaLytic, in particular in B16 and MC38 models, independently of combination with PD-1 blockade. Importantly, these increases were not offset by parallel recruitment of regulatory T cells in B16 and EMT6 models. Furthermore, the frequency of the cross-presenting subset of dendritic cells increased after CodaLytic treatment and directly associated with tumor volume (4T1: R2=0.30, p<0.01). A TME conducive to anti-tumor immunity was further supported by recruitment of B, NK and CD4+ T cells.ConclusionsCodaLytic treatment induced changes in the murine tumor immune infiltrate suggesting anti-tumor immune activity independently of the baseline immune contexture associated with the tumor model. This supports the utility of CodaLytic, a codon-modified virus being developed for breast cancer immunovirotherapy, as a valuable component of novel therapeutic regimens.Ethics ApprovalThe animal work in this study was approved after MisPro Biotech Services IACUC review, protocols 2019–01-17-COD-1, 2022-COD-02 and LC 2022-COD-03. MC38 data was generated according to the IACUC guidelines of Champions Oncology.]]></description><subject>Breast cancer</subject><subject>Immunity (Disease)</subject><subject>Immunotherapy</subject><subject>Influenza</subject><subject>Lymphocytes</subject><subject>Regular and Young Investigator Award Abstracts</subject><subject>Tumors</subject><issn>2051-1426</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2023</creationdate><recordtype>article</recordtype><sourceid>9YT</sourceid><sourceid>DOA</sourceid><recordid>eNpNkctu3CAUhlGkSo2meYYide2Gmxm8jEa9jDRSFknWCANusGzjYGg1XWWRvkiVJ8uTBGYSJRvORd_54fAD8BmjrxhTft67qCuCCK2uttebkuQ-QifglKAaV5gR_hGcLUuPEMKIUiHEKXgsyNP9v-04psn_dsHHWxvUvId_XLyFuYDaGz9Vozeuc9ZAN3VDstNfBTOdFrjxRu320emnh_8wU2lQ0S6HybukBhf30HeHMqbRB-jKTbbIuCGGzOYULmmefYiFVFN01Ts0C3wCHzo1LPbsJa7Azfdv15uf1e7yx3ZzsataLNaospRwwY3hliPeKWpb1VFGWN0RbRXWLVk3gtaK6LZttGEEE4GYYVQwymqu6Qpsj7rGq17OwY0q7KVXTh4aPvySKuRNBytbWhPaWU7qhrImn5pxoRqLmVa6oSRrfTlqzcHfJbtE2fsUpvx8SfLP8zVHeXQF6JFqx_4NwEgWR2VxVBYj5aujsthFnwHGHZv4</recordid><startdate>20231101</startdate><enddate>20231101</enddate><creator>Zhao, Yiwen</creator><creator>Jahan, Nusrat</creator><creator>Blagovic, Katarina</creator><creator>Mueller, Steffen</creator><creator>Robert Coleman, J</creator><creator>Kaufmann, Johanna K</creator><general>BMJ Publishing Group Ltd</general><general>BMJ Publishing Group LTD</general><general>BMJ Publishing Group</general><scope>9YT</scope><scope>ACMMV</scope><scope>K9.</scope><scope>DOA</scope></search><sort><creationdate>20231101</creationdate><title>1100 Immunovirotherapy with the codon-modified influenza virus CodaLytic™ modulates the quality of the tumor immune infiltrate in support of anti-tumor immunity</title><author>Zhao, Yiwen ; Jahan, Nusrat ; Blagovic, Katarina ; Mueller, Steffen ; Robert Coleman, J ; Kaufmann, Johanna K</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-b1870-e32686dd6e606fa3ebaf34245f2cea1cb279835a2cbb9cd4212804d43843456c3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2023</creationdate><topic>Breast cancer</topic><topic>Immunity (Disease)</topic><topic>Immunotherapy</topic><topic>Influenza</topic><topic>Lymphocytes</topic><topic>Regular and Young Investigator Award Abstracts</topic><topic>Tumors</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Zhao, Yiwen</creatorcontrib><creatorcontrib>Jahan, Nusrat</creatorcontrib><creatorcontrib>Blagovic, Katarina</creatorcontrib><creatorcontrib>Mueller, Steffen</creatorcontrib><creatorcontrib>Robert Coleman, J</creatorcontrib><creatorcontrib>Kaufmann, Johanna K</creatorcontrib><collection>BMJ Open Access Journals</collection><collection>BMJ Journals:Open Access</collection><collection>ProQuest Health &amp; Medical Complete (Alumni)</collection><collection>Directory of Open Access Journals(OpenAccess)</collection><jtitle>Journal for immunotherapy of cancer</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Zhao, Yiwen</au><au>Jahan, Nusrat</au><au>Blagovic, Katarina</au><au>Mueller, Steffen</au><au>Robert Coleman, J</au><au>Kaufmann, Johanna K</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>1100 Immunovirotherapy with the codon-modified influenza virus CodaLytic™ modulates the quality of the tumor immune infiltrate in support of anti-tumor immunity</atitle><jtitle>Journal for immunotherapy of cancer</jtitle><stitle>J Immunother Cancer</stitle><date>2023-11-01</date><risdate>2023</risdate><volume>11</volume><issue>Suppl 1</issue><spage>A1211</spage><epage>A1211</epage><pages>A1211-A1211</pages><eissn>2051-1426</eissn><abstract><![CDATA[BackgroundVirotherapeutics leverage oncolytic and pro-inflammatory properties to ultimately engage multiple mechanisms of action that lead to holistic modulation of the tumor microenvironment (TME) and induction of anti-tumor immunity. As such, they serve as off-the-shelf in situ cancer vaccines to generate a personalized immune response. We have previously introduced CodaLytic, a codon-modified influenza virus, as an efficient kick-starter of the cancer immunity cycle in several murine models with different baseline immune contexture and in human tumor explant cultures. Here, we are presenting a deeper dive into the immune cell composition infiltrating syngeneic mouse tumors after treatment with CodaLytic.MethodsEffects on the TME were measured after intratumoral administration of 108 PFU CodaLytic as monotherapy and in combination with immune checkpoint blockade (ICB) and/or chemotherapy in orthotopic EMT6 and 4T1 triple-negative breast cancer, subcutaneous B16-F10 melanoma and MC38 colon cancer mouse models. Tumors were harvested and dissociated for characterization of immune infiltrate by flow cytometry after ≥2 doses of virus and after onset of efficacy based on tumor volume in at least one experimental group.ResultsAcross all models, virus treatment increased tumor infiltration with T and antigen-presenting cells, which could be further boosted by addition of ICB. Both total CD3+ T and importantly CD8+ T cells were recruited to tumors in response to treatment and their frequency within the immune infiltrate correlated directly with tumor volumes (CD3+: MC38 R2=0.58, p<0.02; EMT6 R2=0.31, p<0.02; 4T1 R2=0.50, p<0.0001. CD8+: MC38 R2=0.60, p<0.02; EMT6 R2=0.20, p<0.05; 4T1 R2=0.15, p<0.05). Interestingly, addition of ICB further supported the increase of T cell infiltration in alignment with improved efficacy, while Granzyme B expression was primarily driven by CodaLytic, in particular in B16 and MC38 models, independently of combination with PD-1 blockade. Importantly, these increases were not offset by parallel recruitment of regulatory T cells in B16 and EMT6 models. Furthermore, the frequency of the cross-presenting subset of dendritic cells increased after CodaLytic treatment and directly associated with tumor volume (4T1: R2=0.30, p<0.01). A TME conducive to anti-tumor immunity was further supported by recruitment of B, NK and CD4+ T cells.ConclusionsCodaLytic treatment induced changes in the murine tumor immune infiltrate suggesting anti-tumor immune activity independently of the baseline immune contexture associated with the tumor model. This supports the utility of CodaLytic, a codon-modified virus being developed for breast cancer immunovirotherapy, as a valuable component of novel therapeutic regimens.Ethics ApprovalThe animal work in this study was approved after MisPro Biotech Services IACUC review, protocols 2019–01-17-COD-1, 2022-COD-02 and LC 2022-COD-03. MC38 data was generated according to the IACUC guidelines of Champions Oncology.]]></abstract><cop>London</cop><pub>BMJ Publishing Group Ltd</pub><doi>10.1136/jitc-2023-SITC2023.1100</doi><oa>free_for_read</oa></addata></record>
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subjects Breast cancer
Immunity (Disease)
Immunotherapy
Influenza
Lymphocytes
Regular and Young Investigator Award Abstracts
Tumors
title 1100 Immunovirotherapy with the codon-modified influenza virus CodaLytic™ modulates the quality of the tumor immune infiltrate in support of anti-tumor immunity
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