Regular and Young Investigator Award Abstracts最新文献

{"title":"1065 A replication-defective, HSV-1-based gene therapy for localized delivery of combinatorial Interleukins-12 and -2 for the treatment of cutaneous malignancies","authors":"Dana Previte, Mary Jane Duermeyer, Jorge Guzman Lepe, Trevor Parry, Suma Krishnan","doi":"10.1136/jitc-2023-sitc2023.1065","DOIUrl":"https://doi.org/10.1136/jitc-2023-sitc2023.1065","url":null,"abstract":"","PeriodicalId":500964,"journal":{"name":"Regular and Young Investigator Award Abstracts","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135217571","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}

{"title":"634 EVEREST-1: A seamless phase 1/2 study of CEA logic-gated Tmod CAR T-cell therapy (A2B530) in patients with solid tumors associated with CEA expression also exhibiting HLA loss of heterozygosity (LOH)","authors":"Salman R Punekar, Theodore Welling, J Randolph Hecht, Julian Molina, Caleb Smith, Edward Garon, M Pia Morelli, Marwan Fakih, Kedar Kirtane, Patrick M Grierson, Sandip P Patel, Yi Lin, Scott Kopetz, Frederick L Locke, Jeffrey Ward, Ariane Lozac’hmeur, Matthew Frigault, Sarah Nikiforow, Wen-Kai Weng, Jennifer Specht, Tomislav Dragovich, Judy Vong, Armen Mardiros, Kirstin Liechty, William Y Go, John Welch, Eric W Ng, Marcela Maus, David Maloney, Diane M Simeone","doi":"10.1136/jitc-2023-sitc2023.0634","DOIUrl":"https://doi.org/10.1136/jitc-2023-sitc2023.0634","url":null,"abstract":"","PeriodicalId":500964,"journal":{"name":"Regular and Young Investigator Award Abstracts","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135217572","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}

{"title":"64 Augmenting low-plex multiplex imaging by leveraging the potential of same-slide H&E analysis","authors":"Becky Arbiv, Assaf Debby, Nethanel Asher, Guy Ben-Betzalel, Ron Elran, Pinchas Birnbaum, Shai Bookstein, Tal Dankovich, Lena Tsabari, Yuval Shachaf, Yoad Cohen, Amit Bart, Oscar Puig, Kenneth Bloom, Ronnie Shapira-Frommer, Iris Barshack, Ettai Markovits","doi":"10.1136/jitc-2023-sitc2023.0064","DOIUrl":"https://doi.org/10.1136/jitc-2023-sitc2023.0064","url":null,"abstract":"","PeriodicalId":500964,"journal":{"name":"Regular and Young Investigator Award Abstracts","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135217574","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}

{"title":"749 Early phase oncology experience on the use of an oncolytic adenovirus encoding for TNFa and IL-2 for the treatment of solid tumors – Interim results","authors":"Joao Santos, Inge Svane, Katriina Peltola, Tuomo Alanko, Riitta Korpisaari, Susanna Juteau, Marjut Jaakkola, Jorma Sormunen, Juha Kononen, Eva Ellebaek, Tine Monberg, Marco Donia, Amir Khammari, Brigitte Dreno, Santeri A Pakola, James Clubb, Elise Jirovec, Dafne CA Quixabeira, Tatiana Kudling, Lyna Haybout, Victor Cervera-Carrascon, Claudia Kistler, Suvi Sorsa, Riikka Havunen, Akseli Hemminki","doi":"10.1136/jitc-2023-sitc2023.0749","DOIUrl":"https://doi.org/10.1136/jitc-2023-sitc2023.0749","url":null,"abstract":"","PeriodicalId":500964,"journal":{"name":"Regular and Young Investigator Award Abstracts","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135217774","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}

{"title":"1064 Characterization of preclinical anti-tumor and pharmacodynamic activity in response to conditionally active IFNa with or without checkpoint blockade","authors":"Benjamin Povinelli, Kamaljeet Kaur, Alexey Berezhnoy, Hsin Wang, Nicole Lapuyade, Carol LePage, Michael Winter, Olga Vasiljeva, Madan Paidhungat, Vangipuram Rangan, Erwan Le Scolan, Leila Boustany, Marcia Belvin, Dylan Daniel","doi":"10.1136/jitc-2023-sitc2023.1064","DOIUrl":"https://doi.org/10.1136/jitc-2023-sitc2023.1064","url":null,"abstract":"","PeriodicalId":500964,"journal":{"name":"Regular and Young Investigator Award Abstracts","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135217800","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}

{"title":"82 Spatial immunophenotyping of longitudinal metastatic melanoma specimens to identify biomarkers of response and resistance to combination anti-LAG-3 + anti-PD-1-based immunotherapies","authors":"Tuba N Gide, Ella McCutcheon, Nigel Maher, Yizhe Mao, Ping Shang, Alexander M Menzies, Ines Pires da Silva, James S Wilmott, Richard A Scolyer, Georgina V Long","doi":"10.1136/jitc-2023-sitc2023.0082","DOIUrl":"https://doi.org/10.1136/jitc-2023-sitc2023.0082","url":null,"abstract":"","PeriodicalId":500964,"journal":{"name":"Regular and Young Investigator Award Abstracts","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135217837","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}

{"title":"955 Disruption of the circadian clock accelerates colorectal cancer and promotes immunosuppression","authors":"Selma Masri, Bridget Fortin","doi":"10.1136/jitc-2023-sitc2023.0955","DOIUrl":"https://doi.org/10.1136/jitc-2023-sitc2023.0955","url":null,"abstract":"","PeriodicalId":500964,"journal":{"name":"Regular and Young Investigator Award Abstracts","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135217846","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}

{"title":"1270 Predicting risk factors for severe immune-related adverse events requiring hospitalization from checkpoint inhibitors","authors":"Jordyn Silverstein, Michelle Wang, Francis Wright, Joy Huang, Jessica Santhakumar, Eva Duvalyan, Arabella Young, Daniel Kim, Kimberly De Dios, Sam Brondfield, Zoe Quandt","doi":"10.1136/jitc-2023-sitc2023.1270","DOIUrl":"https://doi.org/10.1136/jitc-2023-sitc2023.1270","url":null,"abstract":"<h3>Background</h3> As immune checkpoint inhibitors (CPI) are increasingly approved for the treatment of multiple cancer types, hospitalizations related to severe immune-related adverse events (irAE) will increase in tandem. Here, we identify risk factors that predict hospitalization from an irAE to help guide clinical decision-making for future patients on CPI therapy. <h3>Methods</h3> This retrospective case-control study included patients exposed to CPIs who were hospitalized from 1/2012 to 12/2020 at our tertiary care hospital by computationally extracting data from the electronic health record. We then performed manual chart review to include only confirmed irAE-related hospitalizations. Controls were patients who had received CPI therapy without an irAE hospitalization matched by gender, age and cancer type to the cases. Controls were manually chart reviewed for data abstraction and to confirm there was not an irAE hospitalization. We assessed association of hospitalization with variables of interest using student t and fisher exact as appropriate. We included variables in the multivariate logistic regression analysis that had p < 0.10 in the univariate analysis. <h3>Results</h3> Of 3137 patients treated with CPIs, 114 (3.6%) were hospitalized for irAEs, resulting in 124 hospitalizations. In this preliminary analysis, 158 controls were reviewed. Patients who were hospitalized did not have significant differences in age, gender, race, cancer type, body mass index, Eastern Cooperative Oncology Group (ECOG) performance status, smoking and alcohol history, and Charlson Comorbidity Index (table 1). The hospitalized group had more patients treated with combination therapy (PD-1/L1 and CTLA-4) (33.3% vs 13.3%) and less PD-1/L1 monotherapy (60.5% vs 82.9%) (p=0.001). The hospitalized group also had less prior CPI therapy (12.9% vs 31.0%, p=0.001). Patients hospitalized for an irAE had more pre-existing autoimmune conditions although not statistically significant (13.7% vs 6.9%, p=0.065). After multivariate logistic regression, pre-existing autoimmune condition (OR 2.41, 95% CI: 1.01–5.75 p=0.048) and combination immunotherapy (4.02, 2.13–7.59 p<0.001) was associated with increased odds of hospitalization, while prior CPI therapy was associated with decreased odds (0.32, 0.16–0.65 p=0.001) (table 2). <h3>Conclusions</h3> This real-world data suggest patients who have a pre-existing autoimmune condition or are being treated with combination immunotherapy had higher odds of an irAE hospitalization, while tolerating prior CPI therapy decreased odds of hospitalization. Understanding who is at risk for these events is critical both for weighing the risks and benefits of therapy, monitoring for toxicities, as well as eventually developing treatments that can prevent, modify or treat irAEs. <h3>Ethics Approval</h3> This study was approved by the UCSF Human Research Protection Program [#17–22987].","PeriodicalId":500964,"journal":{"name":"Regular and Young Investigator Award Abstracts","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135161121","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}

{"title":"1103 Spatial mapping and clinical significance of the CD39/CD73 adenosinergic pathway as a candidate immunotherapy target in non-small cell lung cancer","authors":"Kerryan Ashley, Krishna Iyer, Rakesh Kumar, Zachary A Cooper, Roy S Herbst, Sarah Goldberg, Kurt Schalper","doi":"10.1136/jitc-2023-sitc2023.1103","DOIUrl":"https://doi.org/10.1136/jitc-2023-sitc2023.1103","url":null,"abstract":"<h3>Background</h3> The ectonucleotidases CD39 and CD73 act sequentially to convert ATP into highly immunosuppressive adenosine that can accumulate in the extracellular milieu and suppress NK/T-cell anti-tumor responses. Blockade of CD73 in combination with other immunostimulatory antibodies can induce anti-tumor responses in subset of patients with non-small cell lung cancer (NSCLC). The levels, spatial distribution, clinicopathologic associations and biomarker potential of the CD39/CD73 pathway in NSCLC, as well as the impact of chemoradiotherapy, remain poorly understood. <h3>Methods</h3> Using multiplexed quantitative immunofluorescence (mQIF), we simultaneously measured the levels of CD39, CD73 protein, CD8+ T-cells and cytokeratin (CK)-expressing cancer-cells in five retrospective NSCLC cohorts represented in tissue microarrays. The mQIF analysis included compartment-based measurements based on fluorescence co-localization as well as single-cell segmentation/phenotyping and spatial analysis. The first three cohorts included baseline tumor samples from patients with stages I-IV NSCLC treated with non-immunotherapy regimens (Cohort #1, n=179; Cohort #2, n=172; Cohort #3, n=267). The fourth cohort (Cohort #4, n= 68) included baseline tumor samples from patients treated with immunotherapy. The fifth cohort (Cohort #5, n=23 pairs) included paired biopsies before and after chemotherapy with or without radiotherapy. Associations between the markers with clinicopathologic variables and outcomes were studied. <h3>Results</h3> 90% of NSCLCs showed detectable concurrent expression of both CD39 and CD73, but the levels were highly variable across cases. CD39+ cell density was higher in nonmalignant CK- stromal cell areas and CD73+ cell density was higher within the CK+ cancer cell nests. The levels of the markers were positively associated across the cohorts and high expression of CD39 or CD73 were consistently associated with higher local CD8+ T-cell infiltration and adenocarcinoma histology. CD8+ T-cells were more distant from CD73+ cancer cells than CD73- cancer cells. After chemoradiotherapy, CD73+ cells are significantly depleted. Stromal CD39+ cells and tumor CD73+ cells were associated with better outcomes after immunotherapy. <h3>Conclusions</h3> The CD39/CD73 pathway is expressed in the majority of NSCLCs with a distinct tumor/stromal cell distribution. This pathway is associated with local adaptive anti-tumor immune responses, adenocarcinoma histology and better outcome after immunotherapy. Chemo-radiotherapy reduces the density of CD73+ expressing cells in the tumor microenvironment without significantly altering the spatial distribution of these cells relative to CD8+ TILs. <h3>Acknowledgements</h3> Funding Source: AstraZeneca","PeriodicalId":500964,"journal":{"name":"Regular and Young Investigator Award Abstracts","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135161125","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}

{"title":"1458 TTLL8, POTEE, and PKMYT1 are targetable tumor antigens in ovarian cancer","authors":"Esen Yonca Bassoy, Remya Raja, Tom Rubino, Fabian Coscia, Krista Goergen, Brenda Ernst, Paul Magtibay, Kristina Butler, Alessandra Schmitt, Ann Oberg, Marion Curtis","doi":"10.1136/jitc-2023-sitc2023.1458","DOIUrl":"https://doi.org/10.1136/jitc-2023-sitc2023.1458","url":null,"abstract":"<h3>Background</h3> High-grade serous ovarian cancer (OC) is the most common and lethal subtype, with a 70% mortality rate and an 85% relapse rate within five years.¹Cancer testes (CT) antigens are tumor-associated antigens with restricted expression in immune-privileged tissues, as well as abnormal expression in cancer.² This indicates that they can be targeted for their immunogenicity without the risk of toxicity to normal tissue. Currently, few antigens have been validated for OC. We thus hypothesized that the use of immunopeptidomics could reveal novel CT antigens that can be targeted for OC treatment. <h3>Methods</h3> Immunopeptidomics was performed with the HLA-A2:01-positive OVCAR-5 cell line, and identified 10,197 peptides corresponding to 5,604 unique proteins. NetMHCcons was used to generate consensus affinity values for each peptide and identified high-confidence HLA-A02:01-restricted peptides. The expression profiles of each protein were analyzed in the Human Protein Atlas database. Tissue microarrays containing 120 patient samples were stained via immunohistochemistry (IHC) to assess tumor expression levels and survival analysis was carried out. Primary human T cell samples were stimulated with peptide candidates and intracellular cytokine staining (IC), tetramer-staining, and T cell killing assays against peptide-pulsed OC cells were performed. <h3>Results</h3> We performed immunopeptidomics on an OC cell line that expresses the common HLA-A02:01 haplotype to find possible new tumor antigens that could be used as immunotherapy targets. From this dataset, we identified TTLL8, POTEE, and PKMYT1 peptides as candidate tumor antigens. Using tissue microarrays, TTLL8 was found to be expressed in 60% of OC and was significantly associated with a worse overall prognosis. POTEE was expressed in over 90% of OC patients and had no significant association with survival. Expression of POTEE was increased in OC cell lines by treatment with a DNA methyltransferase inhibitor as is characteristic of many CT antigens. In patient tumor samples, TTLL8-, POTEE-, and PKMYT1-specific CD8 T cell responses were identified by increases in cytokine production and tetramer-positive populations. TTLL8-, POTEE-, and PKMYT1-specific T cells induced tumor cell killing of antigen pulsed OC cells. The use of a blocking antibody targeting MHC class I demonstrated that the T cell-induced killing was dependent on CD8 T cell recognition of antigen. <h3>Conclusions</h3> These results suggest that TTLL8, POTEE, and PKMYT1 are good targets for the development of antigen-targeted immunotherapy in OC. <h3>Acknowledgements</h3> This study was supported by a Career Enhancement Award (MC) from the Mayo Clinic Ovarian SPORE grant (P50 CA136393). <h3>References</h3> Siegel RL, Miller KD, Fuchs HE, Jemal A. Cancer Statistics. <i>CA: a cancer journal for clinicians</i>, 2021;<b>71</b>(1):7–33. Simpson AJ, Caballero OL, Jungbluth A, Chen YT, Old LJ. Cancer/test","PeriodicalId":500964,"journal":{"name":"Regular and Young Investigator Award Abstracts","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135161126","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}