bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 5181: The role of Neuropilin-1 signaling in CD4 conventional T cell immune function in non-small cell lung cancer
Authors: Kahangi Bitta P. , Lim Raymond J. , Abascal Jensen , Crosson William P. , Reyes Edgar Perez , Dumitras Camelia , Tran Linh M. , Krysan Kostyantyn , Salehi-Rad Ramin , Dubinett Steven M. , Liu Bin 
Published: April 2023

Abstract
Despite advances in therapy, lung cancer remains the leading cause of cancer related deaths. In non-small cell lung cancer (NSCLC), a subset of tumor-infiltrating CD4 T cells express Neuropilin-1 (NRP1), a transmembrane protein that binds to multiple ligands with diverse functions in tumor and immune cells. Recent studies reveal that NRP1 can be induced upon T cell receptor stimulation and that NRP1 signaling promotes increased stabilization and function of CD4+ FoxP3+ regulatory T cells (Tregs), while signaling on CD8 T cells results in inhibition of CD8 T cell migration and cytotoxicity; therefore, NRP1 is implicated as a newly defined immune checkpoint protein. The functional role of NRP1 in CD4+ FoxP3- T conventional cells (CD4 Tconv) and the ligands involved are largely unexplored. We have found that human lung cancer malignant pleural effusions (MPE) from a subset of metastatic lung cancer patients contain both NRP1+ and NRP1- CD4 Tconv cells, providing a relevant clinical setting to study the function of NRP1 in human T cells. Our preliminary studies reveal that MPE-derived NRP1+ CD4 Tconv cells have altered expression of CD25, suggestive of a more activated state as compared to that of NRP1- CD4 Tconv cells. Additionally, we have observed disproportionate cell death of NRP1+ CD4 Tconv cells that can be partially rescued with anti-NRP1 monoclonal antibodies (mAbs). Surviving NRP1+ cells are more likely to express PD-1 and secrete effector cytokines. In our murine NSCLC model carrying key driver mutations KrasG12D P53−/− Lkb1−/− and higher tumor mutational burden (KPL-3M), analysis of tumor-infiltrating CD4 Tconv cells confirm that NRP1+ CD4 T cells are preferentially found within tumors and with higher PD-1 expression as compared to NRP1- cells. Furthermore, treatment with anti-NRP1 mAbs confers anti-tumor efficacy in this model, indicating that NRP1 is a functionally important inhibitor of host anti-tumor immune responses. These data suggest that CD4 Tconv cells expressing NRP1 are activated but prone to cell death, warranting further investigation into its potential as a therapeutic target for NSCLC.
Citation Format: Bitta P. Kahangi, Raymond J. Lim, Jensen Abascal, William P. Crosson, Edgar Perez Reyes, Camelia Dumitras, Linh M. Tran, Kostyantyn Krysan, Ramin Salehi-Rad, Steven M. Dubinett, Bin Liu. The role of Neuropilin-1 signaling in CD4 conventional T cell immune function in non-small cell lung 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 5181.
Abstract 5328: Novel KRAS-specific in-well lysis ELISA for high throughput screening
Authors: Park Hyun Min , Poole Jason , Jelinek Mary Anne 
Published: April 2023

Abstract
RAS is one of the most frequently mutated genes in cancer. Gain–of–function missense mutations promoting oncogenesis cluster at codons 12, 13, and 61 of KRAS, NRAS and HRAS. These result in enhanced GTP binding due to fast exchange of nucleotide and/or impairment of GAP (GTPase Activating Protein) binding. Although these mutants are all activating, they are not equal in their oncogenic potential and differences in patient survival are associated with different RAS mutants and which RAS allele is affected, with KRAS being the most prevalent. Current RAS therapeutic approaches have migrated to be isoform specific. With this in mind, we have developed an activation state specific high throughput screening compatible (HTS) assay that is specific for KRAS. A novel rabbit anti–KRAS recombinant antibody was isolated via cloning of immunoglobulin variable regions from antigen positive B cells isolated from rabbits immunized with a peptide immunogen targeting a region of low homology between the RAS isoforms. Antibody specificity was validated with recombinant HRAS, KRAS and NRAS proteins over a wide concentration range by both immunoblotting and by a bead–based multiplex ELISA where all three RAS isoforms were present. The new assay allows for direct in–well lysis of cells cultured in 96–well plate format, either directly in media or following a PBS wash step. Activated KRAS in the lysate is captured on the assay plate and detected via chemiluminescence using the KRAS specific antibody. Preliminary assay validation has included EGF treatment of HeLa cells to show activation in cells expressing wildtype KRAS and inhibition with the selective non–covalent KRASG12D inhibitor MRTX1133 in Aspc1 cells known to express KRASG12D over a wide range of cell seeding densities. We anticipate that this assay will further the discovery of novel KRAS specific therapeutics.
Citation Format: Hyun Min Park, Jason Poole, Mary Anne Jelinek. Novel KRAS-specific in-well lysis ELISA for high throughput screening. [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 5328.
Abstract 5475: Improved prediction of immunotherapy responses by constitutive neoantigen load and LINE-1 methylation
Authors: Bang Hyoeun , Kim Jeong Yeon , Joe Cheolyong , Kim Kyeonghui , Bang Younghak , Kim Hyemin , Cha Honghi , Oh Eunjoo , Lee Naeun , Shin Inkyung , Noh Seung-Jae , Cho Dae-Yeon , Lee Se-Hoon , Choi Jung Kyoon 
Published: April 2023

Abstract
Previous biomarkers such as PD-L1 expression, tumor mutation burden (TMB), and neoantigen load have limited accuracy in predicting responses to immune checkpoint inhibitor (ICI) therapy. In this work, we propose an improved predictor of ICI responses on the basis of our previous findings on the role of neoantigen functionality and genomic hypomethylation in tumor immunity. Specifically, we developed a metric of constitutive neoantigen load given the association of constitutive neoantigens derived from genes indispensable for cancer growth with favorable clinical responses to ICI (Clin. Transl. Med. 12:e714). A panel that captures somatic mutations on the 300 most essential genes identified by genome-wide screening in ~1,800 pan-cancer cell lines was used. Our DeepNeo algorithm (Nat. Commun. 11:951; Nat. Genet. 2023) was employed to identify T cell-reactive neoantigens from somatic mutations binding patient-matched HLA proteins. Also, considering the role of genomic hypomethylation in inducing resistance of tumors to ICI therapy (Nat. Commun. 10:4278), we developed an assay that estimates genomic hypomethylation by targeted sequencing of LINE-1 elements. Constitutive neoantigen load and LINE-1 methylation status were evaluated in our cohort consisting of 335 lung cancer patients treated with ICIs. As a result, constitutive neoantigen load (HR=0.671; p-value=3.13E-03) and LINE-1 methylation (HR=0.597; p-value=0.012) outperformed PD-L1 (HR=0.74; p-value=0.199), TMB (HR=0.917; p-value=0.511), and the combination of PD-L1 and TMB (HR=0.707; p-value=0.218). The combination of constitutive neoantigen load and LINE-1 methylation (HR=0.245; p-value=1.11E-05) showed even better predictive power. In conclusion, our approach can be used as new companion diagnostics for ICI-based immune-oncology.
Citation Format: Hyoeun Bang, Jeong Yeon Kim, Cheolyong Joe, Kyeonghui Kim, Younghak Bang, Hyemin Kim, Honghi Cha, Eunjoo Oh, Naeun Lee, Inkyung Shin, Seung-Jae Noh, Dae-Yeon Cho, Se-Hoon Lee, Jung Kyoon Choi. Improved prediction of immunotherapy responses by constitutive neoantigen load and LINE-1 methylation. [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 5475.
Abstract 5527: Undergraduate cancer research scholars’ community field experiences encourage community engagement to curb future disparities in the cancer workforce
Authors: Kovacic Melinda Butsch , Nolan Rachael D. , Loyd Melissa , Sauter Sharon , Ramos Karen , Kues John R. 
Published: April 2023

Abstract
Lack of access to cancer prevention, early screening, and treatment, particularly in low socioeconomic, underserved communities, are cited as substantial barriers to improving survivorship. Overcoming the complexity of this problem will require a larger, diverse, and dedicated workforce. Community engagement can lead to greater awareness of and both access and accrual to research. Encouraging trainees understanding of and participation in community engagement early on is one approach to curb cancer research related disparities. The current pipeline of cancer-focused healthcare professionals and researchers that understand, appropriately engage, and connect with their target communities and patient populations is dangerously inadequate. To expand our future culturally competent, cancer-focused workforce, the University of Cincinnati Cancer Center has established the Cancer Research Scholars Program which is supported in part by a National Cancer Institute R25. The program offers to 20-23 undergraduate scholars each year, unique and inspiring paid research opportunities across the cancer continuum and educational experiences that included cancer topics, professional development, team science, and both cultural humility and microaggression training. Importantly, all scholars prepare for and participate in one of three community-engaged, cancer-focused summer field experiences offered with our community partners to encourage the supporting of and//or active participation in community-engaged research, education, and outreach in their future cancer careers. Twelve of the 23 summer 2022 Scholars were also invited to continue their research into the academic year either in-person or virtually. After year 1, Scholars and mentors completed surveys and on-camera interviews about the program highlighting the program’s successes as well as areas for improvement. Nearly all Scholars appreciated the community engagement opportunities offered and understood their value to their potential careers. Annual tracking of these Scholars will determine the program’s longer-term impact on the cancer workforce.
Citation Format: Melinda Butsch Kovacic, Rachael D. Nolan, Melissa Loyd, Sharon Sauter, Karen Ramos, John R. Kues. Undergraduate cancer research scholars’ community field experiences encourage community engagement to curb future disparities in the cancer workforce. [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 5527.
Abstract 5540: Spouse caregivers of patients with glioblastoma report unmet needs throughout the disease trajectory
Authors: Coman Diana L. , Chard Megan , Desautels Lisa , Lutz Barbara J. , Minns Laurie 
Published: April 2023

Abstract
Glioblastoma (GBM) is a devastating and terminal cancer that results in memory loss, cognitive declines, personality changes, neuropsychiatric symptoms, and physical impairments that greatly affect quality of life of both the patient with GBM and their primary caregiver, who is often a spouse or partner. These caregivers describe feeling unsupported and unprepared to assume the responsibilities associated with addressing the progressive physical, emotional, and psychological support needs of their loved ones with GBM. In this qualitative study, female spouse primary caregivers were recruited through a private Facebook support group to write letters describing their experiences in caring for their loved ones with GBM. Using a reflexive thematic analysis, 101 letters from caregivers were analyzed for unmet needs, challenges, and opportunities for better care and support. Caregivers expressed feeling unsupported and poorly prepared, and described different levels and types of needs and challenges throughout the GBM disease trajectory. The 4 phases of the trajectory included the acute phase (first 2-4 months post diagnosis), living with disease progression, end of life stage, and the bereavement stage. Challenges included difficulties adapting to sudden life changes, the need for more education on what to expect, feelings of sudden loss, relationship strain, and not having enough knowledge about GBM. Associated emotional responses included feelings of fear, lack of control, agony, disappointment, and exhaustion. These challenges and emotional impact were greatest during the acute and living with disease progression phases. Caregivers also described relying heavily on friends, community supports (such as faith groups), peer-support through the Facebook group during this living with disease progression phase, but still experienced high levels of relationship strain and other unmet needs. These findings on the primary caregivers’ experiences provide opportunities to guide more timely and tailored interventions to provide support and improve care for patient/caregiver dyads to help mitigate the burden of this progressive disease and improve quality of life for caregivers.
Citation Format: Diana L. Coman, Megan Chard, Lisa Desautels, Barbara J. Lutz, Laurie Minns. Spouse caregivers of patients with glioblastoma report unmet needs throughout the disease trajectory. [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 5540.
Abstract 5567: Circulating bacterial DNA is a non-invasive biomarker for early recurrence of NSCLC patients
Authors: Chen Haiming , Lu Yiming , Qiu Mantang 
Published: April 2023

Abstract
Background: Alteration of human microbiota has been implicated in non-small cell lung cancer (NSCLC). However, most metagenomics studies utilized fecal samples, circulating bacteria DNA in patients with respectable NSCLC remain unexplored. This study aimed to characterize bacteria DNA in plasma of respectable NSCLC patients and build a machine-learning model to detect early recurrence of NSCLC.
Methods: We performed whole genome sequencing of plasma from 101 NSCLC patients with (n = 36, R) or without (n = 65, NR) tumor recurrence within three years after surgery. Microbial DNA was obtained by removing the host genome and relative abundance was measured by mapping reads into microbial genomes. Significant microbial features were identified in the discovery set and built into a random forest model, which was tested in the validation set.
Results: We enrolled 22 R and 39 NR patients with matching demographic features in the discovery set. The remaining 14 R and 26 NR patients were included in the validation set. PCoA analysis using Bray-Curtis distance showed significant differences between R and NR patients at genus level and species level in the discovery set. Notably, in the discovery set, 4 genera and 13 species showed significantly lower abundance in R patients, whereas 11 genera and 21 species were conversely enriched. Based on these significant microbial features, the random-forest model obtained the maximal AUC value of 0.9044 (95% CI, 0.8203-0.9886) when 11 features were selected. In the validation set, this model distinguished R from NR patients with an AUC of 0. 8434 (95% CI, 0.7189-0.9679).
Conclusions: This pioneer study characterized alteration of circulating bacterial DNA in NSCLC patients with early recurrence, and illustrated significant difference in microbial composition between R and NR patients. The predictive model constructed with selected circulating microbial features was an accurate and non-invasive tool for prediction in early NSCLC recurrence.
Citation Format: Haiming Chen, Yiming Lu, Mantang Qiu. Circulating bacterial DNA is a non-invasive biomarker for early recurrence of NSCLC patients. [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 5567.
Abstract 5662: Early unwanted immunogenicity assessment of immuno oncology drugs
Authors: Pattyn Sofie , Vlaming Martijn , Pieters Alanah , Schockaert Jana 
Published: April 2023

Abstract
Bispecifics targeting multiple antigens or epitopes have been showing great promise for treatment of cancer. However, managing unwanted immunogenicity has become a challenge in the development cycle of these promising therapeutics as there is a trend towards higher unwanted immune responses compared with classical monoclonal antibodies. In vitro assays using human primary immune cells can be used to assess the risk of induction of a cytokine release storm or induction of unwanted immunogenicity. For the latter, T cell activation and proliferation assays can be used to assess and predict an unwanted immune response and avoid induction of anti-drug antibodies later on. In order to achieve reliable and consistent results, high quality primary immune cells should be used in combination with sensitive fit-for-purpose in vitro assays.
Citation Format: Sofie Pattyn, Martijn Vlaming, Alanah Pieters, Jana Schockaert. Early unwanted immunogenicity assessment of immuno oncology drugs. [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 5662.
Abstract 5677: MB101, a novel PD-L1 x CD3 targeted bispecific antibody, exhibits potent tumor-killing efficacy with minimal off-tumor toxicity
Authors: Kim Suna , Bang Hyojoo , Jung Yongjun , Cho Sunjung , Kim Youngsam , Park Sang-hyun , Kang Seok Chan , Park Youngjin , Jung Sungyoub 
Published: April 2023

Abstract
Bispecific antibody (bsAb) which targets tumor-associated antigens and simultaneously induces CD3-mediated T cell activation, is one of the promising therapeutic approaches for cancer treatment. However, despite numerous CD3-based bsAb have been developed, the clinical application faces pronounced hurdles, such as increased on-target off-tumor toxicity and cytokine release syndrome (CRS) by using high-affinity anti-CD3 moieties. Accordingly, there are still needs for the development of CD3-based bsAb with more favorable properties, which are tumor-specific targeting and potent tumor killing activity without excessive cytokine release. Thus, we developed MB101, a novel PD-L1 x CD3 bsAb with low affinity to CD3, which is uncoupled potent tumor cytotoxicity from severe cytokine release. MB101 showed a strong binding affinity to PD-L1 (KD = 0.4 nM) but a weak binding affinity to CD3 (KD = 1.0 μM), indicating preferentially targeting to PD-L1+ tumor cells. MB101 showed an effective tumor cell killing activity with higher Emax compared to avelumab mono- or combination treatment with CD3 mAb in PD-L1+ MDA-MB-231 cells. T cell-mediated cytotoxicity stimulated by MB101 in co-culture with target cells was accompanied by lower secretion of pro-inflammatory cytokines than CD3 mAb and bsAb comparator with high-affinity anti-CD3 arm. Additionally, in the absence of target cells, MB101 treatment to PBMC induced a very low level of pro-inflammatory cytokines, suggesting the possibility of reduced CRS risk. Furthermore, we proved that T cell-mediated cytotoxicity by MB101 was increased in a PD-L1 expression-dependent manner of tumor cells, but not normal cells, indicating minimal on-target off-tumor toxicity. Consistently with in vitro results, MB101 effectively regressed tumor volume (TGI=83%) without induction of excessive cytokine release in human CD3 knock-in mouse model. In addition, MB101 showed superior tumor growth inhibition (TGI=70%) than that of avelumab (TGI=44%) in humanized mouse xenograft model. In summary, MB101 selectively triggers robust PD-L1-dependent tumor cytotoxicity while inducing very low cytokine release, suggesting that MB101 might be a promising therapeutic option as CD3-based bsAb for cancer treatment.
Citation Format: Suna Kim, Hyojoo Bang, Yongjun Jung, Sunjung Cho, Youngsam Kim, Sang-hyun Park, Seok Chan Kang, Youngjin Park, Sungyoub Jung. MB101, a novel PD-L1 x CD3 targeted bispecific antibody, exhibits potent tumor-killing efficacy with minimal off-tumor 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 5677.
Abstract 5792: The novel therapeutic diiminoquinone exhibits anticancer effects on human prostate cancer cells in 2D and 3D in vitro models
Authors: Yehya Amani , Monzer Alissar , Wakimian Kevork , Ghamlouche Fatima , Saheb Nour , Tawil Ayman , Gali-Muhtasib Hala , Mukherji Deborah , El-Hajj Albert , Abou-Kheir Wassim G. 
Published: April 2023

Abstract
Aim: To investigate the anticancer potential of the novel quinone DIQ on prostate cancer (PCa) cells in two-dimensional (2D) and three-dimensional (3D) in vitro.
Methods: The anti-proliferative effect of DIQ on PC3 and DU145 PCa cell lines was determined in vitro by using 3-(4,5 dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and trypan blue exclusion assays. In addition, the potency of DIQ was tested on the formation and size of PCa cell-derived prostatospheres and organoids grown in a specialized 3D-culture system. Also, 3D organoids were established from fresh tissue samples representing different stages of PCa obtained from consented patients who underwent radical prostatectomy at the American University of Beirut Medical Center (AUBMC) according to appropriate Institutional Review Board (IRB) approval guidelines. This model was used to assess DIQ
individualized tumor response on organoids growth and the effect was evaluated by quantifying the number of organoids formed (OFC) and calculating the average size (diameters).
Results: Our results showed that DIQ significantly attenuated cell proliferation and viability in PC3 and DU145 PCa cell lines. DIQ also reduced the formation ability and size of PC3 and DU145 prostatospheres and organoids at sub-toxic doses of 1 µM. Potently, DIQ displayed a significant decrease in both the count and the size of the different patient-derived organoids as compared to their respective control.
Conclusion: This study provides promising clues for the use of the novel anticancer therapeutic DIQ in targeting CSCs, findings that may have promising therapeutic implications for PCa patients.
Citation Format: Amani Yehya, Alissar Monzer, Kevork Wakimian, Fatima Ghamlouche, Nour Saheb, Ayman Tawil, Hala Gali-Muhtasib, Deborah Mukherji, Albert El-Hajj, Wassim G. Abou-Kheir. The novel therapeutic diiminoquinone exhibits anticancer effects on human prostate cancer cells in 2D and 3D in vitro models [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 5792.