Regular and Young Investigator Award Abstracts最新文献

178 Targeting ER-mitochondrial dynamics to improve responses to immune checkpoint blockade 178靶向er -线粒体动力学改善免疫检查点阻断反应

Regular and Young Investigator Award Abstracts Pub Date : 2022-11-01 DOI: 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

引用次数: 0

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 AGEN1423是一种抗cd73 - tgf β- trap双功能抗体，在晚期胰腺癌患者中与balstilimumab联合化疗或不化疗的651期2期试验

Regular and Young Investigator Award Abstracts Pub Date : 2022-11-01 DOI: 10.1136/jitc-2022-sitc2022.0651

J. Grossman, Jaymin Patel, Bonnie L. Bullock, B. Morin, Lilian Gaynor, Manuel Hidalgo, B. Bockorny

引用次数: 1

377 Adoptive cell therapy with cytokine-induced killer cells retargeted with immunotools against HER-2 positive breast cancer 377细胞因子诱导杀伤细胞免疫工具重靶向HER-2阳性乳腺癌的过继细胞治疗

Regular and Young Investigator Award Abstracts Pub Date : 2022-11-01 DOI: 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

引用次数: 0

1014 Complement C3 deficiency increases the anti-tumor immunity of NK cells and controls tumor growth 1014补体C3缺乏增加NK细胞抗肿瘤免疫，控制肿瘤生长

Regular and Young Investigator Award Abstracts Pub Date : 2022-11-01 DOI: 10.1136/jitc-2022-sitc2022.1014

G. Lal, Pradipta Pal, S. Paul, H. T. Meitei, Praneet Wahi, A. Sahu

引用次数: 0

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 SUPLEXA治疗细胞用于转移性实体瘤和血液恶性肿瘤患者的1期、首次人体、开放标签单药研究的临床更新

Regular and Young Investigator Award Abstracts Pub Date : 2022-11-01 DOI: 10.1136/jitc-2022-sitc2022.0632

Rohit Joshi, J. Goh, W. Joubert, Vineet Kwarta, M. Okera, S. Bishnoi, J. Lederer, F. Borriello, S. Gargosky

引用次数: 0

1292 A reproducible pipeline for analysis of multiplex imaging (MIBI) data with application to uncovering novel features of the tumor-immune microenvironment 1292用于多重成像(MIBI)数据分析的可重复管道，用于揭示肿瘤免疫微环境的新特征

Regular and Young Investigator Award Abstracts Pub Date : 2022-11-01 DOI: 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

{"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}

引用次数: 0

717 Interim clinical update of the phase 1b trial of ATRC-101 as monotherapy or in combination with pembrolizumab for select advanced solid tumors 717 ATRC-101单药或联合派姆单抗治疗晚期实体瘤1b期试验中期临床更新

Regular and Young Investigator Award Abstracts Pub Date : 2022-11-01 DOI: 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

引用次数: 0

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 1325 JANX007的临床前活性和安全性，这是一种新的psma靶向肿瘤激活T细胞接触器，用于治疗转移性去势抵抗性前列腺癌

Regular and Young Investigator Award Abstracts Pub Date : 2022-11-01 DOI: 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

{"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}

引用次数: 1

686 Mechanism of action of LAVA-051, a bispecific Vγ9Vδ2 T-cell engager (bsTCE), confirmed in the clinical setting 686双特异性Vγ9Vδ2 t细胞接合剂(bsTCE) LAVA-051的作用机制在临床环境中得到证实

Regular and Young Investigator Award Abstracts Pub Date : 2022-11-01 DOI: 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

{"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}

引用次数: 0

960 TT-816, a novel small molecule immune checkpoint inhibitor targeting cannabinoid CB2receptor, stimulates innate and adaptive immunity for cancer therapy 960 TT-816是一种新型的小分子免疫检查点抑制剂，靶向大麻素cb2受体，刺激先天和适应性免疫用于癌症治疗

Regular and Young Investigator Award Abstracts Pub Date : 2022-11-01 DOI: 10.1136/jitc-2022-sitc2022.0960

P. Fan, E. Elzein, L. Yao

{"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}

引用次数: 0