bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 1779: Fourth-generation chimeric antigen receptor T cells targeting mucin 1 against breast cancer
Authors: Supimon Kamonlapat , Sangsuwannukul Thanich , Junking Mutita , Yenchitsomanus Pa-thai 
Published: April 2023

Abstract
Breast cancer (BC) is the most common cause of deaths worldwide, which is required effective treatment strategies. The second-generation chimeric antigen receptor (CAR) T cell therapy was approved by U.S. Food and Drug Administration for hematological malignancies, exhibiting impressive efficacy. However, CAR T cell therapy has not been approved in solid tumors and it has intensively been the subjects of research and development. To develop CAR T cell therapy, it is crucial to identify target antigen specifically expressed on tumor cells. Mucin 1 (MUC1) was previously reported to be overexpressed in several tumors. In this study, we examined MUC1 expression in BC tissues and cultured cell lines, and to improve CAR T cell efficiency, we generated fourth-generation anti-MUC1 CAR T cells (αM.CAR4 T cells), containing anti-MUC1 single-chain variable fragment (scFv), three costimulatory molecules (CD28, CD137, CD27) and CD3ζ. High levels of MUC1 expression were observed in the tissues and cell lines. Comparing to second- and third-generations (αM.CAR2 T and αM.CAR3 T cells), the αM.CAR4 T cells showed greater proliferation in the CAR T cell production process. The anti-tumor functions of all CAR T cells were specific to MUC1 expression since their killing activities were illustrated against MUC1-positive but not MUC1-negative BC cells. Interestingly, at low effector to target ratios, the αM.CAR4 T cells exhibited higher tumor cell lysis than those of αM.CAR2 T and αM.CAR3 T cells. Furthermore, after exposure to MUC1-positive BC cells, the αM.CAR4 T cells expressed lower programmed cell death protein 1 (PD-1) level. Taken together, the αM.CAR4 T cells are potential to be further developed for treatments of MUC1-positive BC and other cancers.
Citation Format: Kamonlapat Supimon, Thanich Sangsuwannukul, Mutita Junking, Pa-thai Yenchitsomanus. Fourth-generation chimeric antigen receptor T cells targeting mucin 1 against breast cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 1779.
Abstract 1799: BH3120, a bispecific antibody targeting 4-1BB and PD-L1 simultaneously, stimulates T cells in tumor tissue preferred manner
Authors: Wang Jing , Wang Jun , Liu Yang , Pang Yan , Zhang Aihong , Feng Jie , Sun Aibo , Ma Xiao , Cai Jingmei , Xu Jiangcheng , Liu Jiawang , Lee Kyoungwoo 
Published: April 2023

Abstract
BH3120 is a heterodimeric bispecific antibody, designed to target 4-1BB and PD-L1 simultaneously with Pentambody™ platform, to stimulate anti-tumor immune response in a tumor microenvironment (TME) specific manner.
BH3120 showed strong antitumor efficacy in multiple tumor models, and combination of BH3120 with a PD-1 antagonist showed synergic effects eradicating tumor. While BH3120 consistently activates T cells, both as a monotherapy and in combination with a PD-1 antagonist, modulation of immune system in the tumor tissue is clearly de-coupled from that in peripheral blood, suggesting reduced risks of immune related adverse events (irAEs) with BH3120. To verify this hypothesis, BH3120 was compared with reference bispecific antibodies. Combination of BH3120 with a PD-1 antogonist does not result in elevation of transaminase enzymes, while the reference bispecific antibodies, when combined with the same PD-1 antagonist, show significant increase of the enzymes and macrophage in liver.
In the toxicology studies conducted so far with cynomolgus monkeys, NOAEL of BH3120 was determined to be 200 mg/kg (QW X 5).
Citation Format: Jing Wang, Jun Wang, Yang Liu, Yan Pang, Aihong Zhang, Jie Feng, Aibo Sun, Xiao Ma, Jingmei Cai, Jiangcheng Xu, Jiawang Liu, Kyoungwoo Lee. BH3120, a bispecific antibody targeting 4-1BB and PD-L1 simultaneously, stimulates T cells in tumor tissue preferred manner [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 1799.
Abstract 18: Transcriptomic analysis of mucinous adenocarcinoma in genetically-engineered mouse model
Authors: Sada Haruki , Niitsu Hiroaki , Nakahara Hikaru , Miguchi Masashi , Sakamoto Naoya , Oue Naohide , Tashiro Hirotaka , Ohdan Hideki , Hinoi Takao 
Published: April 2023

Abstract
Background and Aim: The nature and characteristic of human mucinous colorectal adenocarcinomas have not been well elucidated yet. We previously reported a genetically-engineered mouse model for colonic neoplasia producing mucin based on inactivation of Transforming Growth Factor β Receptor Type II (Tgfbr2) and Apc (CDX2P-G19Cre;Apc flox/+;Tgfbr2flox/flox), which is useful to investigate the mechanism of tumor formation. This mouse model developed colonic neoplasia from 12 weeks of age. Despite the same genotype, 40% of the tumors were found mucinous adenocarcinoma and 28% were high-grade adenoma. For further investigation, we herein perform transcriptomic analysis to clarify the molecular differences in these two histologically different tumors.
Method: Total RNA were extracted from mucinous adenocarcinomas and high-grade adenomas in CDX2P-G19Cre;Apcflox/+;Tgfbr2 flox/flox mice from fresh frozen tumors (n=3, each). Then, RNA-seq and Gene Set Enrichment Analysis were performed. Samples were sequenced on NovaSeq 6000, and gene sets queried included the Hallmark.
Results: Mucinous adenocarcinoma and high-grade dysplasia were differentially clustered in principal component analysis despite the same genotype. Gene set enrichment analysis showed 19 upregulated signaling pathways including KRAS signaling and epithelial mesenchymal transition, and 8 suppressed signaling pathways including E2F targets and MYC targets in mucinous adenocarcinoma compared to high-grade dysplasia (FDR &lt; 0.05).
Conclusions: By comparing transcriptome of mucinous adenocarcinoma with high-grade adenoma in our mouse model, 27 differential signal pathways were detected. Some of these pathways are presumably associated with the nature and the characteristics of mucinous adenocarcinoma. We are further investigating the effects of these differences in signal pathways and the correlation with human mucinous adenocarcinoma.
Citation Format: Haruki Sada, Hiroaki Niitsu, Hikaru Nakahara, Masashi Miguchi, Naoya Sakamoto, Naohide Oue, Hirotaka Tashiro, Hideki Ohdan, Takao Hinoi. Transcriptomic analysis of mucinous adenocarcinoma in genetically-engineered mouse model [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 18.
Abstract 1833: Novel IL-12 Partial Agonist For Cancer Immunotherapy Avoids NK-cell Mediated Toxicity
Authors: Koliesnik Ievgen , Emmerich Jan , Tran Kim Q. , Bauer Michele , Totagrande Michael , Jayaraman Bhargavi , Buffone Cindy , Balasubrahmanyam Priyanka , Rokkam Deepti , Malefyt Rene de Waal , Zuniga Luis , Greb Heiko , Ratti Navneet , Vivona Sandro , Oft Martin , Lupardus Patrick J. , Kastelein Robert A. 
Published: April 2023

Abstract
Here we report on a novel human IL-12 partial agonist (hIL-12v) that has diminished binding to IL-12Rb1. IL-12v is designed to more selectively engage antigen activated T-cells, which strongly upregulate IL-12Rb1 upon activation, and to reduce stimulation of NK cells or resting T cells, which express modest levels of IL-12Rb1. To explore anti-tumor efficacy and toxicity in mouse syngeneic tumor models, we generated a half-life extended mouse surrogate of the IL-12 partial agonist (mIL-12v Fc) and compared it to a similarly engineered half-life extended version of wild type mouse IL-12 (mIL-12wt Fc). At efficacious doses, systemic administration of mIL-12wt Fc induced significant weight loss and lethality characterized by early proinflammatory cytokine release and systemic NK cell activation. Conversely, mIL-12v Fc was well tolerated and avoided the robust and rapid NK cell activation and peripheral NK count decreases seen with mIL-12v Fc, suggestive of extravasation to tissues. Both mIL-12v Fc and mIL-12 WT Fc showed similar robust single-agent anti-tumor efficacy in syngeneic tumor models. Depletion of NK cells did not diminish anti-tumor efficacy. Efficacy for both molecules was characterized by CD8 T cell activation, myeloid cell reprograming and antigen presentation. Moreover, combination of mIL-12v Fc with systemic immunotherapies further enhanced anti-tumor activity without compromising tolerability. Overall, mIL-12v Fc retained anti-tumor efficacy without induction of severe toxicities compared to mIL-12wt Fc. These data suggest IL-12 partial agonists may represent a novel immunotherapy approach to maintain efficacy while avoiding classical toxicity associated with IL-12 therapy.1 Atkins, et al.; (1997) Clinical Cancer Research 3(3):409-172 Carson, et al. (1999) J Immunology 162 (8): 4943-4951.
Citation Format: Ievgen Koliesnik, Jan Emmerich, Kim Q. Tran, Michele Bauer, Michael Totagrande, Bhargavi Jayaraman, Cindy Buffone, Priyanka Balasubrahmanyam, Deepti Rokkam, Rene de Waal Malefyt, Luis Zuniga, Heiko Greb, Navneet Ratti, Sandro Vivona, Martin Oft, Patrick J. Lupardus, Robert A. Kastelein. Novel IL-12 Partial Agonist For Cancer Immunotherapy Avoids NK-cell Mediated Toxicity [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 1833.
Abstract 1879: A novel dual CAB nectin-4 x CD3 bispecific antibody targeting solid tumors
Authors: Lucas Matthew , Cugnetti Ana Paula , Liu Haizhen , Xing Charles , Wang Jing , McNeeley Patricia , Wheeler Christina , Joyner Solmarie , Johnson Kyrie , Woodard Kathryn , Zhou Wei , Chang Cathy , Frey Gerhard , Boyle William J. , Short Jay M. 
Published: April 2023

Abstract
Nectin-4 is a Ca2+ independent immunoglobulin-like protein that is primarily involved in cell-cell adhesion. Nectin-4 is overexpressed in several tumor types, including breast, lung, urothelial, colorectal, pancreatic, and ovarian cancers. Overexpression of Nectin-4 is associated with multiple aspects of tumor progression such as proliferation, angiogenesis, epithelial to mesenchymal transition, metastasis, DNA repair and tumor relapse. This overexpression is correlated with poor prognosis, making Nectin-4 an attractive target for developing new therapeutic strategies for cancer. As a result, a substantial number of antibody drug conjugates targeting Nectin-4 are under development. Most of these therapies, however, display a high rate of drug related toxicities accentuating the need for alternative approaches for anti-cancer therapeutics targeting Nectin-4. We leveraged BioAtla’s Conditionally Active Biologic (CAB) platform to develop a dual CAB T cell engager (TCE) bispecific antibody targeting Nectin-4 and CD3 receptors (CAB-Nectin-4 x CAB-CD3 bispecific antibody). The dual CAB Nectin-4 x CD3 bispecific antibody was engineered to bind with high affinity to both Nectin-4 and CD3 receptor antigens under conditions that mimic the acidic tumor microenvironment, but with lower binding activity in physiological (alkaline) conditions. In vitro and in vivo efficacy data for a dual-CAB Nectin-4 x CD3 bispecific antibody will be presented. Our data will demonstrate that the dual-CAB bispecific antibody promotes cytotoxicity of Nectin-4-expressing cancer cells in vitro and induces complete tumor regression in vivo. Further, the dual CAB Nectin-4 x CD3 bispecific antibody has higher potency in inducing primary T cell activation measured by means of cytokine release and cancer cell cytotoxicity under acidic conditions compared to the non-CAB benchmark bispecific antibody.
Citation Format: Matthew Lucas, Ana Paula Cugnetti, Haizhen Liu, Charles Xing, Jing Wang, Patricia McNeeley, Christina Wheeler, Solmarie Joyner, Kyrie Johnson, Kathryn Woodard, Wei Zhou, Cathy Chang, Gerhard Frey, William J. Boyle, Jay M. Short. A novel dual CAB nectin-4 x CD3 bispecific antibody targeting solid tumors [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 1879.
Abstract 1967: Addressing breast cancer disparities: knowledge and attitudes towards cancer prevention through breastfeeding among African American women in Georgia
Authors: Vernon Marlo M. 
Published: April 2023

Abstract
Background: A qualitative needs assessment was conducted to inform the development of a culturally competent breast and ovarian cancer prevention intervention, through the promotion of breastfeeding (BF) and genetic screening for cancer risk among African American (AA) women. In Georgia, AA women are diagnosed with later-stage breast/ovarian cancer and have higher mortality rates. BF initiation and longer duration are associated with reduced risk of cancers, yet BF rates are lower among AA women and few BF promotion programs are culturally competent.
Methods: 20 AA Mothers (Age: 18-25y=40%, 25-29y=40%, 31-35y=20%; Edu: ≤HS=60%; # of children: 1=40%) who were either pregnant (n= 9, 45%) or within the first year postpartum (n= 11, 55%), were interviewed. Questions assessed BF intentions and prior experiences, knowledge of BF preventing cancer, familial breast/ovarian cancer risk, best promotion practices, and genetic screening attitudes.
Results: Mothers (70%) reported previous BF initiation, with 65% reporting 6wks as the longest BF duration. No mother reported knowing that BF can prevent cancer. When asked about their own risk of cancer, a quarter of mothers reported knowing they were at risk of breast or ovarian cancer; a large majority (85%) were open to genetic screening and wanted to know their genetic risk for cancer. Mothers identified two themes: education and help/peer support to improve BF initiation and duration. There were no differences in responses based on demographics, BF experience, parity, or pregnancy/postpartum.
Discussion: Results confirm a lack of knowledge of the cancer risk reduction conferred by BF. Women reported significant support for genetic screening and a need for education and peer social support for BF; these results will inform intergenerational cancer prevention education efforts.
Citation Format: Marlo M. Vernon. Addressing breast cancer disparities: knowledge and attitudes towards cancer prevention through breastfeeding among African American women in Georgia [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 1967.
Abstract 1976: Lung cancer screening disparities in Southeastern U.S
Authors: Rivers Desiree A. 
Published: April 2023

Abstract
Purpose: In Alabama, lung cancer is the leading cause of cancer death. High lung cancer incidence and mortality rates are attributed to high smoking rates among underserved, low income, and rural populations. Rural residents in Alabama tend to be older, engage in risky health behaviors, and have lower adherence to preventive care than do their urban and suburban counterparts. Disparities in mortality rates between rural and urban areas are particularly large for lung cancer. It can be explained by increased tobacco use and the preponderance of late-stage diagnoses following the lack of uptake of LCS. Therefore, we examined factors associated with LCS uptake among patients who were referred to screening at University of Alabama at Birmingham (UAB) from 2015-2020.
Method: A retrospective cohort of individuals seen at UAB who were eligible for lung cancer screening from 01/01/2015 and 12/31/2020 was used to define the cohort. Included individuals were 55-80 years old, without diagnostic codes for lung cancer (ICD9 162.9 or ICD10 C34.90 within the past 10 years), and a history of smoking: Patient demographic variables included Age; Sex; Race/Ethnicity; distance from UAB and RUCA codes. Chi-square tests and Student t-tests was used to compare screening uptake across patient demographic and clinical variables. We used bivariate analyses to determine significant predictors of lung cancer screening uptake at UAB.
Results: 67355 were identified as eligible for LCS of whom 1147 were screened, 16 individuals were not AL residents and therefore were not included in further analysis. Of those 1129 individuals screened, mean age was 67.02, male (54.92%) and Non-Hispanic White (57.77%). When compared to those who were not screened(97.86%), those screened were more likely to have live in an urbanized area (2.14%). Additionally, when compared to those who were not screened (48.16 mi), those screened were more likely to live closer to UAB (28.67 mi).
Conclusion: LCS has not reached all subgroups; additional targeted efforts are essential to increase lung cancer screening uptake.
Citation Format: Desiree A. Rivers. Lung cancer screening disparities in Southeastern U.S [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 1976.
Abstract 2054: Whole-genome sequencing based homologous recombination deficiency testing for precision oncology of breast cancers
Authors: Kim Ryul , Park Seongyeol , Lim Joonoh , Yi Boram , Koo Jaemo , Lee Sangmoon , Lee Jeong Seok , Park Yeon Hee , Ju Young Seok 
Published: April 2023

Abstract
Breast cancers (BCs) with defects in homologous recombination repair (HRR) pathway depend on the Poly (ADP-ribose) polymerase enzymes (PARP) for their survival and thus are sensitive to PARP inhibitors (PARPi). To screen out BCs with homologous recombination deficiency (HRD), germline mutations in BRCA genes have been tested, which constitute approximately 5% of unselected BC patients. However, a substantial proportion of BCs show HRD phenotypes despite the absence of BRCA inactivating mutations in germline. Herein, we apply whole-genome sequencing (WGS) and whole-transcriptome sequencing (WTS) in 332 samples from 325 BC patients for characterizing their HRD phenotypes for PARPi treatments. Of 325 BC patients, 75 cases (23.1%) showed remarkable HRD phenotypes, based on mutational signatures of HRR abrogation. Intriguingly, 51 cases do not harbor any germline mutations in HR-related genes including BRCA1 and BRCA2. The whole-genome portrait of these samples was similar to that of HRD-positive BCs with
germline mutation in HRR pathway, but showed markedly distinctive features from HRD-negative BCs. With a notable exception of BRCA1, the second most common somatic mutation in HRD-positive BCs without germline mutation, the mutational landscape of the whole study samples was primarily determined by hormone receptor and HER2 positivity, not by HRD status. Likewise, WTS-based clusters determined in an unsupervised manner were highly dependent on the histological subtype of BC, not on HRD status or germline mutations in the HRR pathway. Notably, differentially expressed gene and gene set enrichment analysis revealed that HRD-positive BCs had an increased inflammatory activity compared to BCs with proficient HR. Overall, our analysis demonstrate that WGS enables better classification of the HR status in BC than conventional BRCA germline testing, suggesting WGS as a rapid and sensitive tool for screening breast cancers for PARPi treatment.
Citation Format: Ryul Kim, Seongyeol Park, Joonoh Lim, Boram Yi, Jaemo Koo, Sangmoon Lee, Jeong Seok Lee, Yeon Hee Park, Young Seok Ju. Whole-genome sequencing based homologous recombination deficiency testing for precision oncology of breast cancers [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 2054.
Abstract 2224: Applying optical genome mapping to detect genomic biomarkers and use for residual disease monitoring in hematologic malignancies
Authors: Chitsazan Alex , Pang Andy , Hastie Alex 
Published: April 2023

Abstract
Disease monitoring is important to detect cancer relapse, often as a result of a treatment-surviving cancer cell population. Detection of relapse is critical to determine the intensity and length of treatments and to predict the outcome of those treatments. Currently, karyotyping, fluorescent in situ hybridization (FISH), flow cytometry, PCR, and next-generation sequencing (NGS) are often used for this application. PCR is sensitive and highly effective, but as a targeted approach, it requires the identification of an appropriate biomarker. Karyotyping and FISH are used to follow structural variants, especially those detected at diagnosis and known to be drivers of carcinogenesis; however, karyotype has low sensitivity (~5-10% variant allele frequency (VAF)) and FISH is only targeted.We describe a novel workflow to find structural variants (SVs) using optical genome mapping (OGM) and to use those SVs as biomarkers for disease monitoring assessment. The initial SV profile from a cancer sample can be obtained by running the standard somatic workflow for OGM: 1.5 Tbp of high molecular genomic DNA is collected (without any amplification/selection), and molecules that can capture SV breakpoints are locally assembled into genome maps. These locally assembled genome maps are used to make high-confidence SV calls at least 5 kbp in size. Then, presumptive somatic variants are revealed by further comparison against an OGM control sample SV database (included in Bionano Access/Solve software). Subsequently, to detect residual cancer cells post-treatment, an ultra-deep coverage of approximately 5 Tbp of DNA can be collected, and these molecules are directly aligned to the genome maps in the initial cancer sample. This direct alignment approach is fast and sensitive in identifying remnants of pretreatment originator cells. We are currently applying this workflow to recover known leukemia-associated inter-chromosomal translocations, and our preliminary results indicate a sensitivity of detecting calls at a minimum of 0.5% VAF. Continual investigation on limit of detection is ongoing, but with the improvement on throughput and algorithms, we envision that this workflow to be essential in discovering low level clonal cancerous DNA.
Citation Format: Alex Chitsazan, Andy Pang, Alex Hastie. Applying optical genome mapping to detect genomic biomarkers and use for residual disease monitoring in hematologic malignancies [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 2224.