Pub Date : 2022-11-01DOI: 10.1136/jitc-2022-sitc2022.0324
J. Copland, Kendall J Schick, J. Gleba, T. Huynh, James Miller, Erin Miller, A. A. Demirer, Erin E Tapper, R. Sakemura, Elizabeth L. Siegler, Michelle J. Cox, Carli M. Stewart, Ismail Can, Ekene J. Ogbodo, C. Roman, Bezerra Evandro, Cui Gaofeng, Mer Georges, Olivier Gloria, Yushi Qui, R. Smallridge, A. Zubair, H. Tun, S. Kenderian
{"title":"324 Sensitizing poorly differentiated thyroid cancers to TSHR-CART cell therapy with MEK inhibitors","authors":"J. Copland, Kendall J Schick, J. Gleba, T. Huynh, James Miller, Erin Miller, A. A. Demirer, Erin E Tapper, R. Sakemura, Elizabeth L. Siegler, Michelle J. Cox, Carli M. Stewart, Ismail Can, Ekene J. Ogbodo, C. Roman, Bezerra Evandro, Cui Gaofeng, Mer Georges, Olivier Gloria, Yushi Qui, R. Smallridge, A. Zubair, H. Tun, S. Kenderian","doi":"10.1136/jitc-2022-sitc2022.0324","DOIUrl":"https://doi.org/10.1136/jitc-2022-sitc2022.0324","url":null,"abstract":"","PeriodicalId":398566,"journal":{"name":"Regular and Young Investigator Award Abstracts","volume":"15 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":"130510201","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-sitc2022.0369
C. Passaro, Balázs Koscsó, Sean Smith, Violet Young, Theresa Ross, Benjamin Primack, N. Ly, Patricia Timpug, S. Davoodi, R. Burga, Gauri Kulkarni, Scott Lajoie, M. Langley, Nirzari Shah, Dexue Sun, Daniel Li, R. Duan, Arman Aksoy, M. Khattar, J. Tchaicha, D. Sethi, J. Meulen, M. Ols
{"title":"369 Enhancers of innate and adaptive immunity combine with membrane bound IL15 to increase the efficacy of tumor infiltrating lymphocyte (TIL) therapy for tumors with immunosuppressive microenvironments","authors":"C. Passaro, Balázs Koscsó, Sean Smith, Violet Young, Theresa Ross, Benjamin Primack, N. Ly, Patricia Timpug, S. Davoodi, R. Burga, Gauri Kulkarni, Scott Lajoie, M. Langley, Nirzari Shah, Dexue Sun, Daniel Li, R. Duan, Arman Aksoy, M. Khattar, J. Tchaicha, D. Sethi, J. Meulen, M. Ols","doi":"10.1136/jitc-2022-sitc2022.0369","DOIUrl":"https://doi.org/10.1136/jitc-2022-sitc2022.0369","url":null,"abstract":"","PeriodicalId":398566,"journal":{"name":"Regular and Young Investigator Award Abstracts","volume":"86 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":"126778027","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-sitc2022.0706
O. Bechter, J. Martín-Liberal, A. D’Alise, G. Leoni, G. Cotugno, L. Siani, Rosa Vitale, Valentino Ruzza, E. Micarelli, Irene Garzia, T. Faivre, S. Gogov, P. Delaite, S. Colloca, Maria Ambrosio, R. Merone, E. Scarselli, S. Symeonides
{"title":"706 NOUS-PEV, a novel personalized viral-based prime/boost cancer immunotherapy targeting patient-specific neoantigens: interim results from the first subjects in the phase 1b study","authors":"O. Bechter, J. Martín-Liberal, A. D’Alise, G. Leoni, G. Cotugno, L. Siani, Rosa Vitale, Valentino Ruzza, E. Micarelli, Irene Garzia, T. Faivre, S. Gogov, P. Delaite, S. Colloca, Maria Ambrosio, R. Merone, E. Scarselli, S. Symeonides","doi":"10.1136/jitc-2022-sitc2022.0706","DOIUrl":"https://doi.org/10.1136/jitc-2022-sitc2022.0706","url":null,"abstract":"","PeriodicalId":398566,"journal":{"name":"Regular and Young Investigator Award Abstracts","volume":"20 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":"126789891","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-sitc2022.0886
Yong-Chul Moon, Mithun Gosh, H. An, Tae Hoen Kim, Sa Deok Hong, N. Katuwal, Minsil Kang
{"title":"886 Combined allogeneic NK cell and Herzuma® is effective in HER2-low breast cancer preclinical model by enhancing antibody-dependent cellular cytotoxicity","authors":"Yong-Chul Moon, Mithun Gosh, H. An, Tae Hoen Kim, Sa Deok Hong, N. Katuwal, Minsil Kang","doi":"10.1136/jitc-2022-sitc2022.0886","DOIUrl":"https://doi.org/10.1136/jitc-2022-sitc2022.0886","url":null,"abstract":"","PeriodicalId":398566,"journal":{"name":"Regular and Young Investigator Award Abstracts","volume":"36 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":"126960380","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-sitc2022.0033
Nuthchaya Mejun, N. Leelayuwatanakul, Pongsakorn Ouwongprayoon, C. Vinayanuwattikun, N. Hirankarn
{"title":"33 Role of plasma T-cell-derived circulating DNA level in anti-PD(L)1 immunotherapy in advanced stage non-small cell lung cancer","authors":"Nuthchaya Mejun, N. Leelayuwatanakul, Pongsakorn Ouwongprayoon, C. Vinayanuwattikun, N. Hirankarn","doi":"10.1136/jitc-2022-sitc2022.0033","DOIUrl":"https://doi.org/10.1136/jitc-2022-sitc2022.0033","url":null,"abstract":"","PeriodicalId":398566,"journal":{"name":"Regular and Young Investigator Award Abstracts","volume":"4 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":"129037977","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-sitc2022.0638
M. Pelster, M. Gordon, Justin Moser, T. Wise-Draper, J. C. Park, W. Iams, R. Zwirtes, J. Jennings, N. Miselis, Rui-Ru Ji, S. Loughhead, H. Bernstein, A. Sharei, A. Jimeno
{"title":"638 COMMANDER-001: a phase 1/2, first-in-human, multicenter, open label study of SQZ-eAPC-HPV as monotherapy and with pembrolizumab in patients with HPV16+ recurrent, locally advanced, or metastatic solid tumors (trial in progress)","authors":"M. Pelster, M. Gordon, Justin Moser, T. Wise-Draper, J. C. Park, W. Iams, R. Zwirtes, J. Jennings, N. Miselis, Rui-Ru Ji, S. Loughhead, H. Bernstein, A. Sharei, A. Jimeno","doi":"10.1136/jitc-2022-sitc2022.0638","DOIUrl":"https://doi.org/10.1136/jitc-2022-sitc2022.0638","url":null,"abstract":"","PeriodicalId":398566,"journal":{"name":"Regular and Young Investigator Award Abstracts","volume":"56 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":"130576951","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-sitc2022.1194
Maryam M Bhatti, M. Weiss, Amanda R. Haltom, Jessica Finn, A. Gai, Anne Ye, Danhui Zhang, C. Czupalla, A. Stuparu, Yvonne Leung, E. Wechsler, Iraz T. Aydin, D. Emerling, A. Manning-Boğ, N. Vad, Alexander Scholz, Philippe Marguet, S. Lippow
Background Eph proteins are the largest family of receptor tyrosine kinases in humans and are normally involved in cell-to-cell communication, plasticity, and patterning. EphA2 repre-sents an attractive therapeutic target due to its overexpression in many cancers. Unfortunately, to date, clinical efforts to target EphA2 have demonstrated limited efficacy or significant toxicity. Methods We sequenced the antibody chains expressed by sin-gle plasmablast B cells from patients with cancer and identified antibodies selectively binding to non-autologous human tumor tissues. The target and epitope of an antibody of inter-est were identified by FACS, yeast display, and crystallography methods. Lead optimization used sequence- and structure-based rational mutations, combined with selections from high-throughput yeast display screening. Optimized leads were engi-neered into several weaponized formats and tested for safety and anti-tumor activity. assays. Optimized leads demonstrated tumor-selective binding across multiple tumor types and labeling of plasma membranes and cytoplasmic puncta. Antibody weaponization in multiple formats
{"title":"1194 Discovery and pre-clinical development of a novel and differentiated EphA2-targeted antibody in multiple bispecific formats","authors":"Maryam M Bhatti, M. Weiss, Amanda R. Haltom, Jessica Finn, A. Gai, Anne Ye, Danhui Zhang, C. Czupalla, A. Stuparu, Yvonne Leung, E. Wechsler, Iraz T. Aydin, D. Emerling, A. Manning-Boğ, N. Vad, Alexander Scholz, Philippe Marguet, S. Lippow","doi":"10.1136/jitc-2022-sitc2022.1194","DOIUrl":"https://doi.org/10.1136/jitc-2022-sitc2022.1194","url":null,"abstract":"Background Eph proteins are the largest family of receptor tyrosine kinases in humans and are normally involved in cell-to-cell communication, plasticity, and patterning. EphA2 repre-sents an attractive therapeutic target due to its overexpression in many cancers. Unfortunately, to date, clinical efforts to target EphA2 have demonstrated limited efficacy or significant toxicity. Methods We sequenced the antibody chains expressed by sin-gle plasmablast B cells from patients with cancer and identified antibodies selectively binding to non-autologous human tumor tissues. The target and epitope of an antibody of inter-est were identified by FACS, yeast display, and crystallography methods. Lead optimization used sequence- and structure-based rational mutations, combined with selections from high-throughput yeast display screening. Optimized leads were engi-neered into several weaponized formats and tested for safety and anti-tumor activity. assays. Optimized leads demonstrated tumor-selective binding across multiple tumor types and labeling of plasma membranes and cytoplasmic puncta. Antibody weaponization in multiple formats","PeriodicalId":398566,"journal":{"name":"Regular and Young Investigator Award Abstracts","volume":"225 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":"123361904","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-sitc2022.1092
K. Moynihan, Danielle C. Pappas, H. Sultan, Terrence Park, Manu Kumar, Ruth Lan, Irene Ni, Jessie M. Chen, M. Chin, T. Schumacher, A. Yeung, R. Schreiber, I. Djuretic
Background AB248 is a fusion of an affinity-attenuated IL-2 mutein and an antibody targeting CD8+ T cells designed to overcome the limitations of wild-type IL-2 and second-genera-tion IL-2R bg agonists, “ not- a ” IL-2 and IL-15 variants. Like “ not- a ” IL-2, AB248 ’ s IL-2 mutein does not bind IL-2R a and thus avoids IL-2R a -associated vascular leak syndrome (VLS) and preferential Treg activation in nonclinical models. Further, the IL-2 mutein in AB248 has reduced IL-2R b affinity, and its cis-targeting to CD8+ T cells enables AB248 to avoid the biased expansion of IL-2R b high NK cells and IL2R bg -mediated activation of Tregs associated with untargeted IL2R bg agonists. Thus, AB248 ’ s design enables robust IL-2 pharmacology on CD8+ T cells, key effectors with IL-2-based therapy 1-2 , while avoiding cell types that may promote toxicity or oppose antitumor activity. Here, the mechanisms by which AB248 achieves enhanced nonclinical activity and safety profiles over untargeted IL-2-based therapies are elucidated. sorted PBMC subsets interrogated this and necessity of dual IL-2R a and IL-2R bg affinity reduction as well as CD8+ T cell cis-targeting to avoid antigen-independent cytokine release. Strong anti-tumor activity elicited by muAB248 multiple murine
{"title":"1092 The CD8+ T cell selectivity of AB248 is essential for optimal anti-tumor activity and safety in nonclinical models","authors":"K. Moynihan, Danielle C. Pappas, H. Sultan, Terrence Park, Manu Kumar, Ruth Lan, Irene Ni, Jessie M. Chen, M. Chin, T. Schumacher, A. Yeung, R. Schreiber, I. Djuretic","doi":"10.1136/jitc-2022-sitc2022.1092","DOIUrl":"https://doi.org/10.1136/jitc-2022-sitc2022.1092","url":null,"abstract":"Background AB248 is a fusion of an affinity-attenuated IL-2 mutein and an antibody targeting CD8+ T cells designed to overcome the limitations of wild-type IL-2 and second-genera-tion IL-2R bg agonists, “ not- a ” IL-2 and IL-15 variants. Like “ not- a ” IL-2, AB248 ’ s IL-2 mutein does not bind IL-2R a and thus avoids IL-2R a -associated vascular leak syndrome (VLS) and preferential Treg activation in nonclinical models. Further, the IL-2 mutein in AB248 has reduced IL-2R b affinity, and its cis-targeting to CD8+ T cells enables AB248 to avoid the biased expansion of IL-2R b high NK cells and IL2R bg -mediated activation of Tregs associated with untargeted IL2R bg agonists. Thus, AB248 ’ s design enables robust IL-2 pharmacology on CD8+ T cells, key effectors with IL-2-based therapy 1-2 , while avoiding cell types that may promote toxicity or oppose antitumor activity. Here, the mechanisms by which AB248 achieves enhanced nonclinical activity and safety profiles over untargeted IL-2-based therapies are elucidated. sorted PBMC subsets interrogated this and necessity of dual IL-2R a and IL-2R bg affinity reduction as well as CD8+ T cell cis-targeting to avoid antigen-independent cytokine release. Strong anti-tumor activity elicited by muAB248 multiple murine","PeriodicalId":398566,"journal":{"name":"Regular and Young Investigator Award Abstracts","volume":"162 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":"123364279","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-sitc2022.1456
A. M. Valderrey, D. Kessler, Sierra Thompson, Xinmin Li, Kai Rau, S. Stern, Nicole Rudkin, K. Margolin, S. Kolker, M. Ascierto
Background Melanoma often metastasizes to the brain, 1 usu-ally with a lethal outcome. Recent studies have reported that systemic immunotherapies (IOT) are effective in patients (pts) with melanoma brain metastases (MBM). 2 3 Nevertheless, the failure of IOT in nearly half of patients with MBM leads to the urgency to deeper investigate mechanisms of intrinsic and acquired resistance. The aim of this study is to deeply charac-terize the tumor microenvironment (TME) of primary melanoma (PM) and MBM and to assess inter- and intra-tumor heterogeneity in order to identify potential strategies able to increase the success of IOT in pts with MBM. Formalin-fixed, paraffin-embedded (FFPE) tumor biopsies were derived from 7 PM and 14 MBM biopsies from different pts. was isolated from tumor regions and sub-jected to whole gene expression profiling (GEP). Ingenuity Pathway Analysis (IPA) was performed for enrichment assess-ment, and Microenvironment Cell Populations-counter (MCP-counter) method was used to estimate the abundance of immune and stromal infiltrated cell subpopulations. Selected transcripts including mRNA for CD163, CD45 and CD20 were evaluated by immunohistochemistry (IHC). Inter- and intra-tumor immune heterogeneity of n=59 selected immune protein was also determined in PM and MBM by digital spa-tial profiling (DSP) using Nanostring
{"title":"1456 Characterization of inter and intra tumor heterogeneity in primary melanoma and melanoma brain metastases","authors":"A. M. Valderrey, D. Kessler, Sierra Thompson, Xinmin Li, Kai Rau, S. Stern, Nicole Rudkin, K. Margolin, S. Kolker, M. Ascierto","doi":"10.1136/jitc-2022-sitc2022.1456","DOIUrl":"https://doi.org/10.1136/jitc-2022-sitc2022.1456","url":null,"abstract":"Background Melanoma often metastasizes to the brain, 1 usu-ally with a lethal outcome. Recent studies have reported that systemic immunotherapies (IOT) are effective in patients (pts) with melanoma brain metastases (MBM). 2 3 Nevertheless, the failure of IOT in nearly half of patients with MBM leads to the urgency to deeper investigate mechanisms of intrinsic and acquired resistance. The aim of this study is to deeply charac-terize the tumor microenvironment (TME) of primary melanoma (PM) and MBM and to assess inter- and intra-tumor heterogeneity in order to identify potential strategies able to increase the success of IOT in pts with MBM. Formalin-fixed, paraffin-embedded (FFPE) tumor biopsies were derived from 7 PM and 14 MBM biopsies from different pts. was isolated from tumor regions and sub-jected to whole gene expression profiling (GEP). Ingenuity Pathway Analysis (IPA) was performed for enrichment assess-ment, and Microenvironment Cell Populations-counter (MCP-counter) method was used to estimate the abundance of immune and stromal infiltrated cell subpopulations. Selected transcripts including mRNA for CD163, CD45 and CD20 were evaluated by immunohistochemistry (IHC). Inter- and intra-tumor immune heterogeneity of n=59 selected immune protein was also determined in PM and MBM by digital spa-tial profiling (DSP) using Nanostring","PeriodicalId":398566,"journal":{"name":"Regular and Young Investigator Award Abstracts","volume":"59 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":"123442429","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-sitc2022.0198
M. Herrman, Taylor Barca, X. Yang, M. Tabrizizad, Morgan Smith-Boeck, L. Kiru, Jonathan Wong, Ramandeep Kaur, Smitha Gundurao, Gauri Lamture, A. Azameera, K. Nishimoto, A. Bhat, B. Aftab
{"title":"198 Innate-enhanced chimeric adaptors (CAd): A newly-described approach for augmenting potency of γδ T cell immunotherapy","authors":"M. Herrman, Taylor Barca, X. Yang, M. Tabrizizad, Morgan Smith-Boeck, L. Kiru, Jonathan Wong, Ramandeep Kaur, Smitha Gundurao, Gauri Lamture, A. Azameera, K. Nishimoto, A. Bhat, B. Aftab","doi":"10.1136/jitc-2022-sitc2022.0198","DOIUrl":"https://doi.org/10.1136/jitc-2022-sitc2022.0198","url":null,"abstract":"","PeriodicalId":398566,"journal":{"name":"Regular and Young Investigator Award Abstracts","volume":"83 3 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":"123633341","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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