Pub Date : 2022-11-01DOI: 10.1136/jitc-2022-sitc2022.0178
K. Cook, Elizabeth R. Stirling, Jessica D. Mackert, M. Kooshki, Adam S. Wilson, Wei Zhang, P. Triozzi, David Soto-Pantoja
{"title":"178 Targeting ER-mitochondrial dynamics to improve responses to immune checkpoint blockade","authors":"K. Cook, Elizabeth R. Stirling, Jessica D. Mackert, M. Kooshki, Adam S. Wilson, Wei Zhang, P. Triozzi, David Soto-Pantoja","doi":"10.1136/jitc-2022-sitc2022.0178","DOIUrl":"https://doi.org/10.1136/jitc-2022-sitc2022.0178","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":"115294304","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-sitc2022.0651
J. Grossman, Jaymin Patel, Bonnie L. Bullock, B. Morin, Lilian Gaynor, Manuel Hidalgo, B. Bockorny
{"title":"651 Phase 2 trial of AGEN1423, an anti-CD73-TGFβ-Trap bifunctional antibody, in combination with balstilimab, with or without chemotherapy in subjects with advanced pancreatic cancer","authors":"J. Grossman, Jaymin Patel, Bonnie L. Bullock, B. Morin, Lilian Gaynor, Manuel Hidalgo, B. Bockorny","doi":"10.1136/jitc-2022-sitc2022.0651","DOIUrl":"https://doi.org/10.1136/jitc-2022-sitc2022.0651","url":null,"abstract":"","PeriodicalId":398566,"journal":{"name":"Regular and Young Investigator Award Abstracts","volume":"83 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":"123096711","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-sitc2022.0377
R. Sommaggio, E. Cappuzzello, A. Ventura, S. Perpinello, A. D. Pietà, E. Vigolo, G. D’accardio, P. Palmerini, A. Rosato
{"title":"377 Adoptive cell therapy with cytokine-induced killer cells retargeted with immunotools against HER-2 positive breast cancer","authors":"R. Sommaggio, E. Cappuzzello, A. Ventura, S. Perpinello, A. D. Pietà, E. Vigolo, G. D’accardio, P. Palmerini, A. Rosato","doi":"10.1136/jitc-2022-sitc2022.0377","DOIUrl":"https://doi.org/10.1136/jitc-2022-sitc2022.0377","url":null,"abstract":"","PeriodicalId":398566,"journal":{"name":"Regular and Young Investigator Award Abstracts","volume":"25 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":"121833982","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-sitc2022.1014
G. Lal, Pradipta Pal, S. Paul, H. T. Meitei, Praneet Wahi, A. Sahu
wild-type NK cells. NK cells isolated from tumor-bearing -/- mice showed cytotoxic activity to the NK cells increased secretion of pro-inflammatory cytokines as GM-CSF and IFN-g when with IL-2, IL-15, IL-18 compared to NK cells. Depleting NK cells in -/- mice with anti-NK1.1 mAb significantly prevented the reduction of growth as compared to isotype control IgG mAb.
{"title":"1014 Complement C3 deficiency increases the anti-tumor immunity of NK cells and controls tumor growth","authors":"G. Lal, Pradipta Pal, S. Paul, H. T. Meitei, Praneet Wahi, A. Sahu","doi":"10.1136/jitc-2022-sitc2022.1014","DOIUrl":"https://doi.org/10.1136/jitc-2022-sitc2022.1014","url":null,"abstract":"wild-type NK cells. NK cells isolated from tumor-bearing -/- mice showed cytotoxic activity to the NK cells increased secretion of pro-inflammatory cytokines as GM-CSF and IFN-g when with IL-2, IL-15, IL-18 compared to NK cells. Depleting NK cells in -/- mice with anti-NK1.1 mAb significantly prevented the reduction of growth as compared to isotype control IgG mAb.","PeriodicalId":398566,"journal":{"name":"Regular and Young Investigator Award Abstracts","volume":"164 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":"116640772","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-sitc2022.0632
Rohit Joshi, J. Goh, W. Joubert, Vineet Kwarta, M. Okera, S. Bishnoi, J. Lederer, F. Borriello, S. Gargosky
{"title":"632 Clinical update from a phase 1, first-in-human, open-label single agent study of SUPLEXA therapeutic cells in patients with metastatic solid tumours and haematologic malignancies","authors":"Rohit Joshi, J. Goh, W. Joubert, Vineet Kwarta, M. Okera, S. Bishnoi, J. Lederer, F. Borriello, S. Gargosky","doi":"10.1136/jitc-2022-sitc2022.0632","DOIUrl":"https://doi.org/10.1136/jitc-2022-sitc2022.0632","url":null,"abstract":"","PeriodicalId":398566,"journal":{"name":"Regular and Young Investigator Award Abstracts","volume":"106 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":"116659322","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-sitc2022.1292
Jessica Maxey, Marshall A. Thompson, Katie M. Campbell, B. Kamphaus, Zaid Bustami, Sandra Santulli-Marotto, Daniel K. Wells, S. Boffo, Lisa Salvador, P. Scumpia, Christine N. Spencer, Adam Schoenfeld, Antoni Ribas, L. Kitch
Background Although immune checkpoint inhibition (ICI) has been transformational, tumor-associated factors regulating response have not been elucidated. High-dimensional spatial profiling technologies have enabled simultaneous investigation of many protein targets on individual cells within the spatial context of the tumor microenvironment (TME). Analysis of these data to uncover immune and tumor profiles relies on identification of individual cells and characterization of their specific marker expression to classify lineage and functional state. However, robust automated cell type assignment remains a key challenge in multiplex image data analysis. Here, we describe a reproducible pipeline for single cell identification and typing from multiplex ion beam imaging (MIBI) data uti-lizing lineage protein expression, which has applications in the context of precision immunotherapy and beyond.
{"title":"1292 A reproducible pipeline for analysis of multiplex imaging (MIBI) data with application to uncovering novel features of the tumor-immune microenvironment","authors":"Jessica Maxey, Marshall A. Thompson, Katie M. Campbell, B. Kamphaus, Zaid Bustami, Sandra Santulli-Marotto, Daniel K. Wells, S. Boffo, Lisa Salvador, P. Scumpia, Christine N. Spencer, Adam Schoenfeld, Antoni Ribas, L. Kitch","doi":"10.1136/jitc-2022-sitc2022.1292","DOIUrl":"https://doi.org/10.1136/jitc-2022-sitc2022.1292","url":null,"abstract":"Background Although immune checkpoint inhibition (ICI) has been transformational, tumor-associated factors regulating response have not been elucidated. High-dimensional spatial profiling technologies have enabled simultaneous investigation of many protein targets on individual cells within the spatial context of the tumor microenvironment (TME). Analysis of these data to uncover immune and tumor profiles relies on identification of individual cells and characterization of their specific marker expression to classify lineage and functional state. However, robust automated cell type assignment remains a key challenge in multiplex image data analysis. Here, we describe a reproducible pipeline for single cell identification and typing from multiplex ion beam imaging (MIBI) data uti-lizing lineage protein expression, which has applications in the context of precision immunotherapy and beyond.","PeriodicalId":398566,"journal":{"name":"Regular and Young Investigator Award Abstracts","volume":"33 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":"116677890","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-sitc2022.0717
B. Chmielowski, J. Weroha, S. Ulahannan, J. Powderly, F. Valdes-Albini, T. Bekaii-Saab, D. Doroshow, Alejandro Recio-Boiles, J. Berlin, Yan Xing, S. Khurana, J. Benjamin, S. Isakoff, B. Weinberg
{"title":"717 Interim clinical update of the phase 1b trial of ATRC-101 as monotherapy or in combination with pembrolizumab for select advanced solid tumors","authors":"B. Chmielowski, J. Weroha, S. Ulahannan, J. Powderly, F. Valdes-Albini, T. Bekaii-Saab, D. Doroshow, Alejandro Recio-Boiles, J. Berlin, Yan Xing, S. Khurana, J. Benjamin, S. Isakoff, B. Weinberg","doi":"10.1136/jitc-2022-sitc2022.0717","DOIUrl":"https://doi.org/10.1136/jitc-2022-sitc2022.0717","url":null,"abstract":"","PeriodicalId":398566,"journal":{"name":"Regular and Young Investigator Award Abstracts","volume":"149 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":"116865999","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-sitc2022.1325
Thomas R. DiRaimondo, Natalija Budimir, S. Shenhav, Hua Wu, Vanessa Cicchini, Renee Jocic, Lina Ma, Fabrece Roup, Calvin Campbell, C. Caffaro, Hans Aerni, U. Eskiocak, W. Godfrey, Charles Winter, M. Nasoff, N. Gibson, D. Campbell, Shahram Salek-Ardakani
Background Metastatic castration-resistant prostate cancer (mCRPC) remains an incurable disease. Bispecific T cell engag-ers (TCEs) targeting prostate-specific membrane antigen (PSMA) and CD3 on T cells showed great clinical potential for the treatment of mCRPC. However, cytokine release syn-drome (CRS) and poor pharmacokinetic (PK) profile hinder their further development. To overcome these challenges, Janux has developed JANX007, a tumor-activated T cell engager (TRACTr) with enhanced safety and PK properties. JANX007 is a humanized trispecific protein that contains PSMA- and CD3-binding domains, an albumin binding domain to extend circulating half-life, and a CD3 inhibitory peptide mask fused to the molecule through tumor protease cleavable linker. Only when tumor-resident proteases cleave the TRACTr and enable mask separation can the resulting active molecule bind CD3. This cleavage-dependent CD3 agonism can poten-tially limit systemic toxicity associated with broad T cell activation. Methods Peptide masks against the CD3 binding domain were identified via phage display. Mask efficiency was evaluated using human CD3 ELISAs. Masking and cleavable linker stability was characterized in human (healthy and mCRPC donor) and cynomolgus monkey serum. JANX007-induced cleavage-dependent activation of T cells was evaluated in human PBMC/prostate tumor cell in vitro co-culture assays.
{"title":"1325 Preclinical activity and safety profile of JANX007, a novel PSMA-targeting tumor-activated T Cell engager for treatment of metastatic castration-resistant prostate cancer","authors":"Thomas R. DiRaimondo, Natalija Budimir, S. Shenhav, Hua Wu, Vanessa Cicchini, Renee Jocic, Lina Ma, Fabrece Roup, Calvin Campbell, C. Caffaro, Hans Aerni, U. Eskiocak, W. Godfrey, Charles Winter, M. Nasoff, N. Gibson, D. Campbell, Shahram Salek-Ardakani","doi":"10.1136/jitc-2022-sitc2022.1325","DOIUrl":"https://doi.org/10.1136/jitc-2022-sitc2022.1325","url":null,"abstract":"Background Metastatic castration-resistant prostate cancer (mCRPC) remains an incurable disease. Bispecific T cell engag-ers (TCEs) targeting prostate-specific membrane antigen (PSMA) and CD3 on T cells showed great clinical potential for the treatment of mCRPC. However, cytokine release syn-drome (CRS) and poor pharmacokinetic (PK) profile hinder their further development. To overcome these challenges, Janux has developed JANX007, a tumor-activated T cell engager (TRACTr) with enhanced safety and PK properties. JANX007 is a humanized trispecific protein that contains PSMA- and CD3-binding domains, an albumin binding domain to extend circulating half-life, and a CD3 inhibitory peptide mask fused to the molecule through tumor protease cleavable linker. Only when tumor-resident proteases cleave the TRACTr and enable mask separation can the resulting active molecule bind CD3. This cleavage-dependent CD3 agonism can poten-tially limit systemic toxicity associated with broad T cell activation. Methods Peptide masks against the CD3 binding domain were identified via phage display. Mask efficiency was evaluated using human CD3 ELISAs. Masking and cleavable linker stability was characterized in human (healthy and mCRPC donor) and cynomolgus monkey serum. JANX007-induced cleavage-dependent activation of T cells was evaluated in human PBMC/prostate tumor cell in vitro co-culture assays.","PeriodicalId":398566,"journal":{"name":"Regular and Young Investigator Award Abstracts","volume":"65 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":"116909273","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-sitc2022.0686
Roeland Lameris, J. Ruben, R. Roovers, A. Kater, T. Riedl, V. Iglesias, A. Broijl, I. Tuinhof, S. Umarale, Anton E P Adang, T. D. Gruijl, P. Parren, B. Winograd, H. V. Vliet
Background LAVA-051, a CD1d-targeting first-in-class bispecific single domain antibody (27 kDa), was brought into the clinic based on its high potency antitumor activity through dual engagement of V g 9V d 2-T and iNKT cells, and a low risk of cytokine release syndrome (CRS). Methods A phase 1 study using LAVA-051 is ongoing in patients with relapsed/refractory MM or CLL to determine the recommended phase 2 dose (RP2D). This study has been approved by relevant ethics committees (NCT04887259). A panel of specific pharmacodynamic assays is included to determine the pattern of change in the binding of LAVA-051 to patients ’ peripheral blood V g 9V d 2-T cells (i.e. V g 9V d 2-TCR occupancy) and in the frequency and activation status of V g 9V d 2-T and iNKT cells in circulation. Data presented are focused on the comparison of clinical to pre-clinical observations. Results LAVA-051 triggers V g 9V d 2-T and iNKT cell mediated pro-inflammatory cytokine production, proliferation and antitumor activity in in vitro and ex vivo assays
{"title":"686 Mechanism of action of LAVA-051, a bispecific Vγ9Vδ2 T-cell engager (bsTCE), confirmed in the clinical setting","authors":"Roeland Lameris, J. Ruben, R. Roovers, A. Kater, T. Riedl, V. Iglesias, A. Broijl, I. Tuinhof, S. Umarale, Anton E P Adang, T. D. Gruijl, P. Parren, B. Winograd, H. V. Vliet","doi":"10.1136/jitc-2022-sitc2022.0686","DOIUrl":"https://doi.org/10.1136/jitc-2022-sitc2022.0686","url":null,"abstract":"Background LAVA-051, a CD1d-targeting first-in-class bispecific single domain antibody (27 kDa), was brought into the clinic based on its high potency antitumor activity through dual engagement of V g 9V d 2-T and iNKT cells, and a low risk of cytokine release syndrome (CRS). Methods A phase 1 study using LAVA-051 is ongoing in patients with relapsed/refractory MM or CLL to determine the recommended phase 2 dose (RP2D). This study has been approved by relevant ethics committees (NCT04887259). A panel of specific pharmacodynamic assays is included to determine the pattern of change in the binding of LAVA-051 to patients ’ peripheral blood V g 9V d 2-T cells (i.e. V g 9V d 2-TCR occupancy) and in the frequency and activation status of V g 9V d 2-T and iNKT cells in circulation. Data presented are focused on the comparison of clinical to pre-clinical observations. Results LAVA-051 triggers V g 9V d 2-T and iNKT cell mediated pro-inflammatory cytokine production, proliferation and antitumor activity in in vitro and ex vivo assays","PeriodicalId":398566,"journal":{"name":"Regular and Young Investigator Award Abstracts","volume":"24 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":"117114170","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-sitc2022.0960
P. Fan, E. Elzein, L. Yao
Background The endocannabinoid system is widely expressed in the human body, including the innate and adaptive immune system, where endocannabinoids, D 9-tetrahydrocannabinol and synthetic ligands regulate immune response. The effects of endocannabinoids on immune regulation are primarily medi-ated by G-protein coupled cannabinoid CB 2 receptors (CB 2 R) via several mechanisms, including development, migration, proliferation and effector functions. The upregulated expression of CB 2 R and elevated levels of endocannabinoids have been observed in a variety of tumor microenvironments and are associated with the aggressiveness of cancer. Methods Membranes prepared from CHO-K1 cells stably expressing human CB 2 R were used for receptor binding assays in the presence of TT-816 and [3H]CP-55,940, and for GTP g S binding assay in the presence of TT-816, 10 m M GDP and 0.3 nM [35S]GTP g S. cAMP assay was performed by incu-bating the CHO-K-1 cells for 30 min with TT-816, 25 m M forskolin and 12 nM CP-55,940, or with TT-816 and 5 m M forskolin. NK cell function was determined by co-culturing TT-816 pretreated NK cells with K562 cancer cells for 24 hours. The mixed lymphocyte reaction assay was conducted by co-culturing human CD4+ T cells with monocyte-derived dendritic cells. Cell viability was measured by FACS and IFN-g by MSD. Results TT-816 is a competitive and selective CB 2 R antagonist. human CB an IC50 26.2 nM, showing greater than 380-fold selectivity cannabinoid CB 1 receptors.
内源性大麻素系统在人体内广泛表达，包括先天免疫系统和适应性免疫系统，内源性大麻素、D - 9-四氢大麻酚和合成配体调节免疫反应。内源性大麻素对免疫调节的作用主要是由g蛋白偶联大麻素cb2受体(cb2r)通过发育、迁移、增殖和效应功能等多种机制介导的。在多种肿瘤微环境中观察到cb2r表达上调和内源性大麻素水平升高，并与癌症的侵袭性有关。方法用稳定表达人cb2r的CHO-K1细胞制备膜，在TT-816和[3H]CP-55,940存在下进行受体结合试验，在TT-816、10 m m GTP和0.3 nM [35S]GTP g S存在下进行GTP g S结合试验，将CHO-K-1细胞与TT-816、25 m m福斯克林和12 nM CP-55,940或TT-816和5 m m福斯克林孵卵30 min进行cAMP试验。将TT-816预处理NK细胞与K562癌细胞共培养24小时，测定NK细胞功能。混合淋巴细胞反应试验通过将人CD4+ T细胞与单核细胞来源的树突状细胞共培养进行。FACS法测定细胞活力，MSD法测定IFN-g。结果TT-816是一种竞争性、选择性的cb2r拮抗剂。大麻素cb1受体的IC50值为26.2 nM，具有380倍以上的选择性。
{"title":"960 TT-816, a novel small molecule immune checkpoint inhibitor targeting cannabinoid CB2receptor, stimulates innate and adaptive immunity for cancer therapy","authors":"P. Fan, E. Elzein, L. Yao","doi":"10.1136/jitc-2022-sitc2022.0960","DOIUrl":"https://doi.org/10.1136/jitc-2022-sitc2022.0960","url":null,"abstract":"Background The endocannabinoid system is widely expressed in the human body, including the innate and adaptive immune system, where endocannabinoids, D 9-tetrahydrocannabinol and synthetic ligands regulate immune response. The effects of endocannabinoids on immune regulation are primarily medi-ated by G-protein coupled cannabinoid CB 2 receptors (CB 2 R) via several mechanisms, including development, migration, proliferation and effector functions. The upregulated expression of CB 2 R and elevated levels of endocannabinoids have been observed in a variety of tumor microenvironments and are associated with the aggressiveness of cancer. Methods Membranes prepared from CHO-K1 cells stably expressing human CB 2 R were used for receptor binding assays in the presence of TT-816 and [3H]CP-55,940, and for GTP g S binding assay in the presence of TT-816, 10 m M GDP and 0.3 nM [35S]GTP g S. cAMP assay was performed by incu-bating the CHO-K-1 cells for 30 min with TT-816, 25 m M forskolin and 12 nM CP-55,940, or with TT-816 and 5 m M forskolin. NK cell function was determined by co-culturing TT-816 pretreated NK cells with K562 cancer cells for 24 hours. The mixed lymphocyte reaction assay was conducted by co-culturing human CD4+ T cells with monocyte-derived dendritic cells. Cell viability was measured by FACS and IFN-g by MSD. Results TT-816 is a competitive and selective CB 2 R antagonist. human CB an IC50 26.2 nM, showing greater than 380-fold selectivity cannabinoid CB 1 receptors.","PeriodicalId":398566,"journal":{"name":"Regular and Young Investigator Award Abstracts","volume":"62 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":"121085404","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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