Pub Date : 2022-11-01DOI: 10.1136/jitc-2022-sitc2022.0044
C. Healy, M. Kovacsovics, Natalia Sigal, Li-Chun Cheng, Shane Evans, John Marsiglio, Berit Gibson, Yoko S Derose, Annaleah Larson, Carlos Medina, Jolien M. Sweere, R. Srinivasan, M. Spitzer, J. Hyngstrom, S. Hu-Lieskovan
{"title":"44 Immune signatures of severe immune-related adverse events detected by mass cytometry immune profiling in blood in patients with advanced melanoma treated with immunotherapy","authors":"C. Healy, M. Kovacsovics, Natalia Sigal, Li-Chun Cheng, Shane Evans, John Marsiglio, Berit Gibson, Yoko S Derose, Annaleah Larson, Carlos Medina, Jolien M. Sweere, R. Srinivasan, M. Spitzer, J. Hyngstrom, S. Hu-Lieskovan","doi":"10.1136/jitc-2022-sitc2022.0044","DOIUrl":"https://doi.org/10.1136/jitc-2022-sitc2022.0044","url":null,"abstract":"","PeriodicalId":398566,"journal":{"name":"Regular and Young Investigator Award Abstracts","volume":"73 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2022-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"122548819","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2022-11-01DOI: 10.1136/jitc-2022-sitc2022.0154
M. Stecklum, A. Wulf‐Goldenberg, B. Brzezicha, C. Rupp, W. Walther, J. Hoffmann
Background The preclinical evaluation of many novel immune therapies requires the use mouse models with a functional human immune system. In previous studies we have demonstrated that either peripheral blood mononuclear cells (PBMCs) or subpopulations of PBMCs such as T- and NK-cells or hematopoietic stem cells (HSC) can be used to estab-lish a humanized immune system in immunodeficient mice system with functional T-, B-, and NK cells as well as monocytes and dendritic cells. By transplanting either cell-line or patient-derived tumor xenografts into humanized mice, we successfully generated a fully human tumor-immune-cell model for several tumor entities. Finally, we validated the functionality of these models using either immune-checkpoint inhibitors, cell therapies, or immune cell engagers. either the blood were functional T-cells. Several CDX and PDX models successfully engrafted in these humanized mice without significant differences regarding tumor growth compared to non-human-ized mice. Checkpoint inhibitor treatment led to tumor growth delay in selected models and flow cytometry analysis of tumor samples revealed a high number of tumor infiltrating T-cells. A comparison of checkpoint inhibitor activity in a pan-creatic cancer PDX model using four different humanized mouse models in parallel (HSC, PBMC, T-or NK cell humanized) revealed most convincing results in terms of tumor growth inhibition for the HSC humanized model. Conclusions We have established fully human tumor-immune-cell models for different tumor entities in combination with different donor derived immune cell subsets as effector cells and have demonstrated successful long term engraftment of HSCs. All models have been used for the evaluation of either novel checkpoint inhibitors, cell therapies or immune cell engagers and will allow preclinical and translational studies for the identification of novel therapy options, drug combinations and biomarkers.
{"title":"154 Generation of humanized mouse models for the preclinical evaluation of novel immune checkpoint inhibitors, immune cell engagers and cell therapies","authors":"M. Stecklum, A. Wulf‐Goldenberg, B. Brzezicha, C. Rupp, W. Walther, J. Hoffmann","doi":"10.1136/jitc-2022-sitc2022.0154","DOIUrl":"https://doi.org/10.1136/jitc-2022-sitc2022.0154","url":null,"abstract":"Background The preclinical evaluation of many novel immune therapies requires the use mouse models with a functional human immune system. In previous studies we have demonstrated that either peripheral blood mononuclear cells (PBMCs) or subpopulations of PBMCs such as T- and NK-cells or hematopoietic stem cells (HSC) can be used to estab-lish a humanized immune system in immunodeficient mice system with functional T-, B-, and NK cells as well as monocytes and dendritic cells. By transplanting either cell-line or patient-derived tumor xenografts into humanized mice, we successfully generated a fully human tumor-immune-cell model for several tumor entities. Finally, we validated the functionality of these models using either immune-checkpoint inhibitors, cell therapies, or immune cell engagers. either the blood were functional T-cells. Several CDX and PDX models successfully engrafted in these humanized mice without significant differences regarding tumor growth compared to non-human-ized mice. Checkpoint inhibitor treatment led to tumor growth delay in selected models and flow cytometry analysis of tumor samples revealed a high number of tumor infiltrating T-cells. A comparison of checkpoint inhibitor activity in a pan-creatic cancer PDX model using four different humanized mouse models in parallel (HSC, PBMC, T-or NK cell humanized) revealed most convincing results in terms of tumor growth inhibition for the HSC humanized model. Conclusions We have established fully human tumor-immune-cell models for different tumor entities in combination with different donor derived immune cell subsets as effector cells and have demonstrated successful long term engraftment of HSCs. All models have been used for the evaluation of either novel checkpoint inhibitors, cell therapies or immune cell engagers and will allow preclinical and translational studies for the identification of novel therapy options, drug combinations and biomarkers.","PeriodicalId":398566,"journal":{"name":"Regular and Young Investigator Award Abstracts","volume":"16 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2022-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"122750228","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2022-11-01DOI: 10.1136/jitc-2022-sitc2022.0141
A. Bessede, S. Moulec, J. Guégan, I. Soubeyran, F. Peyraud, C. Rey, A. Italiano
{"title":"141 Indoleamine 2,3 dioxygenase expression predicts response to immune checkpoint blockers in advanced non-small cell lung cancer","authors":"A. Bessede, S. Moulec, J. Guégan, I. Soubeyran, F. Peyraud, C. Rey, A. Italiano","doi":"10.1136/jitc-2022-sitc2022.0141","DOIUrl":"https://doi.org/10.1136/jitc-2022-sitc2022.0141","url":null,"abstract":"","PeriodicalId":398566,"journal":{"name":"Regular and Young Investigator Award Abstracts","volume":"1 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2022-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"122584231","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2022-11-01DOI: 10.1136/jitc-2022-sitc2022.0841
Wilson Guzman, Uli Bialucha, H. Madala, H. Duprey, Manoussa Fanny, Stephanie Hsiao, Parker M. Johnson, Jake Taylor, Rebekah K. O’Donnell, Magali Pederzoli-Ribeil, B. Nicholson, J. O'neil, Caitlin O'Toole
{"title":"841 XTX202, a tumor-selective protein-engineered IL-2, exhibited enhanced anti-tumor activity in combination with checkpoint inhibition in mice","authors":"Wilson Guzman, Uli Bialucha, H. Madala, H. Duprey, Manoussa Fanny, Stephanie Hsiao, Parker M. Johnson, Jake Taylor, Rebekah K. O’Donnell, Magali Pederzoli-Ribeil, B. Nicholson, J. O'neil, Caitlin O'Toole","doi":"10.1136/jitc-2022-sitc2022.0841","DOIUrl":"https://doi.org/10.1136/jitc-2022-sitc2022.0841","url":null,"abstract":"","PeriodicalId":398566,"journal":{"name":"Regular and Young Investigator Award Abstracts","volume":"67 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2022-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"122963077","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2022-11-01DOI: 10.1136/jitc-2022-sitc2022.0976
Jesse Bucksot, D. Lopez-Ramos, Tushar Pandey, A. Antony, Joseph R. Peterson, Daniel J Cook
{"title":"976 T-cell metabolic activity is impacted by the nutrient composition within the tumor microenvironment","authors":"Jesse Bucksot, D. Lopez-Ramos, Tushar Pandey, A. Antony, Joseph R. Peterson, Daniel J Cook","doi":"10.1136/jitc-2022-sitc2022.0976","DOIUrl":"https://doi.org/10.1136/jitc-2022-sitc2022.0976","url":null,"abstract":"","PeriodicalId":398566,"journal":{"name":"Regular and Young Investigator Award Abstracts","volume":"6 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2022-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"123019716","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2022-11-01DOI: 10.1136/jitc-2022-sitc2022.1436
Jacqueline Bersano, Hiren Gosh, E. Oswald, Kanstantsin Lashuk, J. Schueler
{"title":"1436 Modulation of cytokine secretion and macrophage differentiation in a 3D heterotypic spheroid model of colon cancer","authors":"Jacqueline Bersano, Hiren Gosh, E. Oswald, Kanstantsin Lashuk, J. Schueler","doi":"10.1136/jitc-2022-sitc2022.1436","DOIUrl":"https://doi.org/10.1136/jitc-2022-sitc2022.1436","url":null,"abstract":"","PeriodicalId":398566,"journal":{"name":"Regular and Young Investigator Award Abstracts","volume":"73 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2022-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"114298667","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2022-11-01DOI: 10.1136/jitc-2022-sitc2022.0943
Gang Xin, Ruohan Zhang, Bao Zhao, Cankun Wang, Wantong Li, Q. Ma, Nuo Sun, Haitao Wen, William Carson, Zihai Li, A. Ma, Jianying Li
{"title":"943 Harnessing anti-tumor metabolic sensing switch GPR84 on macrophages for cancer immunotherapy","authors":"Gang Xin, Ruohan Zhang, Bao Zhao, Cankun Wang, Wantong Li, Q. Ma, Nuo Sun, Haitao Wen, William Carson, Zihai Li, A. Ma, Jianying Li","doi":"10.1136/jitc-2022-sitc2022.0943","DOIUrl":"https://doi.org/10.1136/jitc-2022-sitc2022.0943","url":null,"abstract":"","PeriodicalId":398566,"journal":{"name":"Regular and Young Investigator Award Abstracts","volume":"11 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2022-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"114515513","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2022-11-01DOI: 10.1136/jitc-2022-sitc2022.1030
J. Hope, Yijuan Zhang, Ashley B. Palete, Hannah A. Faso, S. Roy, D. Otero, Swetha Maganti, C. Commisso, Linda Bradley
cell that the growth of eval-uated if PSGL-1 promotes CD8 + T cell responses to tumors to and
评估PSGL-1是否促进CD8 + T细胞对肿瘤的反应
{"title":"1030 PSGL-1-deficiency suppresses tumor growth of orthotopic pancreatic ductal adenocarcinoma tumors and enhances immune cell infiltration and CD8+T cell responses","authors":"J. Hope, Yijuan Zhang, Ashley B. Palete, Hannah A. Faso, S. Roy, D. Otero, Swetha Maganti, C. Commisso, Linda Bradley","doi":"10.1136/jitc-2022-sitc2022.1030","DOIUrl":"https://doi.org/10.1136/jitc-2022-sitc2022.1030","url":null,"abstract":"cell that the growth of eval-uated if PSGL-1 promotes CD8 + T cell responses to tumors to and","PeriodicalId":398566,"journal":{"name":"Regular and Young Investigator Award Abstracts","volume":"26 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2022-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"121850357","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2022-11-01DOI: 10.1136/jitc-2022-sitc2022.0023
J. Thorlacius-Ussing, N. Willumsen, N. Nissen, C. Jensen, M. Karsdal
{"title":"23 Clues from the matrix – peripheral collagen fragments originating from activity of lymphoid cells, myeloid cells, and fibroblasts may have biomarker potential for cancer immunotherapy","authors":"J. Thorlacius-Ussing, N. Willumsen, N. Nissen, C. Jensen, M. Karsdal","doi":"10.1136/jitc-2022-sitc2022.0023","DOIUrl":"https://doi.org/10.1136/jitc-2022-sitc2022.0023","url":null,"abstract":"","PeriodicalId":398566,"journal":{"name":"Regular and Young Investigator Award Abstracts","volume":"35 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2022-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"122073802","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2022-11-01DOI: 10.1136/jitc-2022-sitc2022.0586
Mingchao Xie, P. Chugh, C. O'Brien, Z. Lai, Ross Stewart, L. Paz-Ares, J. Goldman, M. Garassino, C. Rudin, J. Carl Barrett, Y. Shrestha
{"title":"586 Durvalumab (D) ± tremelimumab (T) + platinum-etoposide (EP) in extensive-stage small-cell lung cancer (ES–SCLC): RNA sequencing analysis to explore canonical markers of IO activity in CASPIAN","authors":"Mingchao Xie, P. Chugh, C. O'Brien, Z. Lai, Ross Stewart, L. Paz-Ares, J. Goldman, M. Garassino, C. Rudin, J. Carl Barrett, Y. Shrestha","doi":"10.1136/jitc-2022-sitc2022.0586","DOIUrl":"https://doi.org/10.1136/jitc-2022-sitc2022.0586","url":null,"abstract":"","PeriodicalId":398566,"journal":{"name":"Regular and Young Investigator Award Abstracts","volume":"39 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2022-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"122078759","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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