tbuckley/cabot-search huggingface dataset:
Abstract 7321: A novel gamma-delta T cell engager platform for cancer immunotherapy
Authors: Lei Ding, Sadhak Sengupta, Mariska ter Haak, Kate Rochlin, Yanjie Li, Lawrence S. Lamb
Journal: Cancer Research (2025)

Abstract Bispecific T cell engagers (TCE) bring effector T cells in contact with cancer cells by binding a pan-T cell receptor sequence and a tumor-associated antigen (TAA) simultaneously, thereby initiating activation and killing properties of the T cell. One of the foremost challenges for the clinical use of TCE is tumor heterogeneity, specifically, the limited expression of specific tumor antigens on the cancer cell surface. Gamma-delta (γδ) T cells are unique in that they recognize multiple stress-associated antigens common to most malignancies regardless of origin. This function is independent of MHC restriction, enabling them to target a broad range of tumors. Here, we report initial findings from a novel γδ T cell engager platform (γδ-TCE), specifically two γδ-TCEs targeting hematologic malignancies, CD33-TCE (CD-33, AML) and CD19-TCE (CD19, B_ALL), while also enabling γδ T cells to engage tumor-associated stress ligands with innate surface receptors such as NKG2D, PVR, and others. Preliminary in vitro characterization revealed properties suggestive of pan-δ chain binding, such as competing with isoprenyl pyrophosphate activation of Vδ2+ T cells, yet efficiently driving both activation and expansion of Vδ1+ and Vδ2+ T cell subsets from peripheral blood mononuclear cells (PBMC). Robust expansion of a diverse repertoire of γδ T cells in the tumor environment is critical for continued pressure and a persistent anti-tumor response. Cytotoxicity assays show that both CD33-TCE and CD19-TCE measurably enhanced γδ T cell-mediated lysis of CD33+ AML and CD19+ ALL tumor cells, respectively, in a dose-dependent manner. In co-cultures with tumor cells, γδ-TCE- armored γδ T cells showed markedly increased degranulation and the release of pro-inflammatory cytokines, such as IFN-γ, TNF-α, granzymes, and perforin, further highlighting the activation of γδ T cells into a potent cytotoxic state and amplifying their tumor-eradicating abilities. This novel γδ T cell engager platform represents a promising new approach to cancer immunotherapy, offering an effective strategy for enhancing γδ T cell-mediated tumor cell lysis. Furthermore, the platform’s modular and flexible design suggests applications in treating a broad range of malignancies by combining the innate recognition properties of γδ T cells with the targeting of specific tumor-associated antigens, thus expanding its therapeutic potential. Citation Format: Lei Ding, Sadhak Sengupta, Mariska ter Haak, Kate Rochlin, Yanjie Li, Lawrence S. Lamb. A novel gamma-delta T cell engager platform for cancer immunotherapy [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 7321.
Abstract 7317: A novel LY6G6D x CD3 bispecific T-cell engager demonstrates better tumor killing and minimal cytokine release than a benchmark molecule
Authors: Lini Huang, Mengting Chen, Yu Zhang, Dong Wu, Shiyong Gong, Xuan Wu, Danqing Wu, Chengbin Wu
Journal: Cancer Research (2025)

Abstract Colorectal cancer (CRC) poses a significant global health challenge with high morbidity and mortality rates. Immune checkpoint inhibitors (ICI) have shown remarkable clinical efficacy in patients with mismatch-repair deficient (dMMR) or microsatellite instability-high (MSI-H) colorectal cancer. However, the vast majority of patients with microsatellite-stable (MSS) or microsatellite instability-low (MSI-L) colorectal cancer cannot benefit from ICI treatment. Recently, lymphocyte Antigen 6 Family Member G6D (LY6G6D) has emerged as a tumor associated antigen selectively expressed in MSS and MSI-low colorectal cancers. By using EpimAb’s proprietary anti-CD3 antibody panel and bispecific antibody platform, we developed EM1034, a novel LY6G6D x CD3 bispecific T-cell engager (TCE). Compared to a clinical stage benchmark TCE which has monovalent target binding arms and asymmetrical knob-into-hole geometry, EM1034 demonstrated hundred folds increased tumor lysis potency while it induced much lower cytokines in vitro. In vivo efficacy studies further demonstrated that EM1034 is more potent than the benchmark molecule in xenografted models with different LY6G6D expression levels. Taken together, this study support EM1034 as a promising molecule for the treatment of mCRC patients with LY6G6D positive MSS/MSI-L tumors. Citation Format: Lini Huang, Mengting Chen, Yu Zhang, Dong Wu, Shiyong Gong, Xuan Wu, Danqing Wu, Chengbin Wu. A novel LY6G6D x CD3 bispecific T-cell engager demonstrates better tumor killing and minimal cytokine release than a benchmark molecule [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 7317.
Abstract 4907: Availability and characteristics of energy balance programs offered by NCI-designated cancer centers
Authors: Jean Miki Reading, Alexandra Rich, Aarifah Bandealy, Payton Solk, Julia Starikovsky, Allegra Frank, Kristina Hasanaj, Shirlene Wang, Siobhan M. Phillips
Journal: Cancer Research (2025)

To broaden our understanding of energy balance programs (diet, physical activity, weight control available for cancer survivors in NCI-designated cancer centers across the United States, we reviewed the characteristics (program components, personalization, delivery mode) of programs using publicly available information on cancer center websites. All NCI-designated cancer centers (n=72 as of 4/24/2024) were included, and two coders reviewed their websites. Each cancer center’s website was searched and reviewed from June 2023 to April 2024. We applied the RE-AIM (Reach, Effectiveness, Adoption, Implementation, Maintenance) framework, an implementation framework used for planning and evaluation of programs, to evaluate each cancer center’s energy balance programming. Information was extracted by each reviewer independently and then checked by a third study staff member for discrepancies. A total of 55 (76%) cancer centers had information on at least one energy balance program or resource posted on their website. These programs included diet/nutrition (n=41), physical activity (n=23), and weight control programs (n=3). Personalized programming was offered in 68% of diet/nutrition programs, 30% of physical activity programs, and 33% of weight control programs. Across all energy balancing behaviors, most programs offered individual sessions (76% diet/nutrition; 57% physical activity; 67% weight control). Group-based support was offered in less than half of programs across all behaviors (29% diet/nutrition; 40% physical activity; 33% weight control). In-person delivery was offered in 56% of diet/nutrition programs, 74% of physical activity programs, and 33% of weight control programs. Most of the programming for cancer survivors addressed diet/nutrition. Weight control programs were limited. Most physical activity programs were delivered in-person, which could limit reach and increase barriers to participation since the median of NCI-designated catchment areas is 26,500 square miles. There is a need for more consistency and availability of personalized support, particularly concerning exercise and weight control. Comprehensively addressing all energy balance components as part of cancer survivorship care is needed. Citation Format: Jean Miki Reading, Alexandra Rich, Aarifah Bandealy, Payton Solk, Julia Starikovsky, Allegra Frank, Kristina Hasanaj, Shirlene Wang, Siobhan M. Phillips. Availability and characteristics of energy balance programs offered by NCI-designated cancer centers [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 4907.
Abstract 2001: Proteomic analysis of plasma exosomes identifies biomarkers for liver and lung metastasis of colorectal cancer patients
Authors: Boyeon Kim, Jwa Hoon Kim, Jiwon Lee, Soohyeon Lee
Journal: Cancer Research (2025)

Abstract Metastasis is the leading cause of mortality in colorectal cancer (CRC), with liver and lung Metastasis being the most common sites of progression. Although early detection of metastasis is crucial for improving patient outcomes, non-invasive predictive strategies remain limited. Exosomes, a class of extracellular vesicles encapsulating cell-derived proteins, DNA, mRNA, and miRNA within a lipid bilayer, closely reflect the molecular characteristics of their originating cells and exhibit exceptional stability in biological samples. These unique features position exosomes as promising candidates for biomarker discovery. In this study, we utilized label-free liquid chromatography-tandem mass spectrometry (LC-MS/MS) to analyze plasma samples from 19 individuals: 5 healthy controls, 7 CRC patients with liver metastasis, and 7 CRC patients with lung metastasis. Blood samples were collected between March 2017 and April 2021, with only plasma from patients who developed metastasis repeatedly and exclusively in the liver or lung during the observation period included in the analysis. From 500 µL of plasma, we extracted an average of 149.9 µg of protein (173.8 µg from healthy controls, 145.9 µg from liver metastasis samples, and 136.8 µg from lung metastasis samples) and identified 851 proteins for further investigation. Our findings revealed that exosomes from CRC patients with metastasis contained elevated levels of proteins associated with angiogenesis, cell differentiation, and cell adhesion—such as ANGPTL6, COL1A1, LAMA2, and RENL—compared to healthy controls. Specifically, VCAN and ANGPTL6 were significantly upregulated in liver metastasis, while CFD and CRTAC1 were highly expressed in lung metastasis. These proteins are known to play critical roles in tumor progression and metastasis across various cancer types. Kaplan-Meier survival analysis based on the mRNA expression levels of these proteins indicated that CRC patients with higher expression exhibited worse overall survival (OS) and relapse-free survival (RFS) compared to those with lower expression levels. Future research will focus on the functional characterization of these identified proteins, the isolation of liver- and lung-specific exosomes, and the identification of small RNA biomarkers. This study represents a significant step toward the development of liquid biopsy-based approaches, particularly leveraging exosomes, for the early prediction of liver and lung metastasis in CRC patients. Citation Format: Boyeon Kim, Jwa Hoon Kim, Jiwon Lee, Soohyeon Lee. Proteomic analysis of plasma exosomes identifies biomarkers for liver and lung metastasis of colorectal cancer patients [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 2001.
Abstract 7320: KGX105, a conditionally active prodrug of EGFRxCD3 T cell engager induces anti-tumor potency
Authors: Yutao Gao, Jing Wang, Shumin Yang, Jie Huang, Hui Chen, Huiping Jiang, Haixiang Wu, Yi Wu, Weidong Jiang
Journal: Cancer Research (2025)

Abstract T cell engagers (TCEs), are highly potent antitumor therapeutics to trigger T cell cytotoxicity, which have shown clinical benefit in hematologic malignancies while far been less successful in solid tumors. The development of TCEs against solid tumors has been limited by the significant on-target toxicity in normal tissues and cytokine release syndrome. Epidermal growth factor receptor (EGFR) is expressed in a variety of solid tumors. Several EGFR-targeted therapeutics have been approved for the treatment of cancer with either limited efficacy or induction of resistance. EGFR-targeting TCEs offered an alternative solution to overcome these issues. To address these challenges, we have developed KGX105, an EGFRxCD3 TCE prodrug with masked EGFR and CD3 antibody, which could be conditionally activated by tumor-specific proteases, and an albumin binding domain to extend the half-life. This design prevents on-target toxicity in normal tissues and systemic activation of T cells in circulation. Once masks are cleaved by tumor microenvironment (TME)-specific proteases, KGX105 could effectively trigger T cell cytotoxicity toward EGFR-positive tumor cells. To confirm KGX105's masking effect, we compared KGX105 and unmasked KGX105 for their ability in binding, T cell activation and T-cell-induced tumor cytotoxicity. KGX105 showed significantly reduced binding to CD3 and EGFR by &amp;gt;1000-fold and &amp;gt;200-fold, compared to the unmasked KGX105. KGX105 also showed reduced potency by &amp;gt;3000-fold in the T cell activation and by &amp;gt;1000-fold in the tumor cell cytotoxicity, which could be fully recovered after protease digestion, comparable to the unmasked KGX105. Then we conducted in vivo antitumor studies in human colorectal cancer HCT116 and COLO205 xenograft models using hPBMC-reconstituted M-NSG mice. KGX105 showed significant anti-tumor efficacy in both tumor models with the TGI% in HCT116 of 95% at 0.3 mg/kg and the TGI% in COLO205 of 68% at 3 mg/kg. No obvious body weight change was observed during the dosing period. The pilot toxic study to evaluate the safety and toxicokinetics of KGX105 is ongoing in Cynomolgus monkeys. The studies presented herein support KGX105 as a promising novel therapeutic to target a wide range of EGFR-expressing cancers with the potential to avoid the life-threatening on-target toxicities and systemic cytokine release. Citation Format: Yutao Gao, Jing Wang, Shumin Yang, Jie Huang, Hui Chen, Huiping Jiang, Haixiang Wu, Yi Wu, Weidong Jiang. KGX105, a conditionally active prodrug of EGFRxCD3 T cell engager induces anti-tumor potency [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 7320.
Abstract 5257: Functional profiling of γδ T cell subsets in malignant pleural effusion and their prognostic value in advanced lung cancer
Authors: Tsai-Tsen Shih, Yi-Chieh Wu, Hsing-Chen Tsai
Journal: Cancer Research (2025)

Abstract The tumor immune microenvironment reflects a patient's immune reserve and offers valuable insights for clinical decision-making. It has the potential to stratify late-stage cancer patients, identifying those likely to benefit from aggressive therapies and those better suited for palliative care. However, obtaining detailed immune profiling from tumor tissues often requires invasive biopsies and poses additional risks. Malignant pleural effusion (MPE), a common complication in advanced lung cancer, provides a minimally invasive alternative for evaluating microenvironmental immune dynamics via thoracentesis. In this study, we analyzed the immune cell composition of malignant pleural effusions (MPE) from 73 patients with late-stage lung adenocarcinoma using high-dimensional spectral flow cytometry and a comprehensive panel of immunophenotypic and functional markers. Our analysis focused on cytotoxic immune cell populations, including NK cells, NKT cells, CD8+ T cells, and γδ T cells. Notably, γδ T cells constituted approximately 1.4% of viable cells, with the Vδ1 and Vδ2 subpopulations representing 32.3% and 46.6% of the γδ T cell compartment, respectively. Higher γδ T cell abundance was associated with shorter overall survival, while no correlation was observed for other immune cell populations. Further analysis revealed that a higher Vδ2/Vδ1 ratio correlated with poorer clinical outcomes. Conversely, elevated expression of the activating receptor DNAM-1 (CD226) on Vδ1 cells was observed in long-term survivors (&amp;gt;2 years) compared to short-term survivors (&amp;lt;6 months), independent of mutation type or treatment modality. These findings were validated using the TCGA lung cancer datasets, confirming a strong link between high DNAM-1 expression and extended survival. In conclusion, γδ T cell subpopulations in MPE, particularly the Vδ1 and Vδ2 subsets, are promising biomarkers for immune fitness and prognosis in advanced lung adenocarcinoma. These results highlight the potential of γδ T cells to identify late-stage patients likely to benefit from aggressive therapies and emphasize the need for larger-scale studies to confirm these findings. Citation Format: Tsai-Tsen Shih, Yi-Chieh Wu, Hsing-Chen Tsai. Functional profiling of γδ T cell subsets in malignant pleural effusion and their prognostic value in advanced lung cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 5257.
Abstract 5289: Mechanisms of metastasis revealed through single-cell spatial transcriptome analysis in patients with liver metastatic colorectal cancer
Authors: Jongwon Lee, Yeseul Kim, Hyo Seon Ryu, Jongmin Sim, Chungyeul Kim, Hyun Woo Kwon, Hyun Je Kim, Jong Min Park, Ah-Reum Lim, Jung Sun Kim, Hwa Jung Sung, Xingyi Guo, Jungmin Choi, Jungyoon Choi
Journal: Cancer Research (2025)

Abstract Background: The efficacy of treating colorectal cancer (CRC) liver metastases is hindered by significant tumor heterogeneity, both within and between tumors. This diversity stems from varied cell populations and complex interactions in the tumor microenvironment, necessitating a deeper understanding of spatial organization and cellular communication patterns. Methods: We examined 23 formalin-fixed paraffin-embedded tissue samples from 11 patients, comprising primary lesions and matched liver metastasis (6 with synchronous and 5 with metachronous metastases) using NanoString 6K CosMx Spatial Molecular Imaging (SMI). Pathologists selected optimal fields of view at tumor invasive fronts. Image processing, cell segmentation, and feature extraction utilized an in-house CosMx SMI pipeline with the Cellpose algorithm. Following quality control, the remaining cells underwent unsupervised clustering with differential gene expression analysis and cell-to-cell interaction analyses performed using the Seurat R package. Results: Analysis of 105, 624 high-quality cells revealed 23 distinct clusters, categorized as ten epithelial tumors, three cancer-associated fibroblast (CAF), two endothelial cells, five immune cells (T cell, Monocyte, Macrophage, SPP1+ Macrophage, and Plasma cell), alveolar cells, hepatocytes, and low complexity cell populations. We identified significant differences in gene expression between colon and liver CAFs, with liver CAFs displaying upregulation of 92 genes associated with epithelial-mesenchymal transition (EMT). Enhanced communication between CAFs, T cells, and macrophages was observed in liver metastases, with specific ligand-receptor pairs (SPP1-ITGA4/ITGB1, LGALS9-P4HB, LGALS9-CD44, CXCL12-CXCR4) enriched in the metastatic microenvironment. Conclusion: Our findings demonstrate distinct spatial heterogeneity and intercellular communication networks in CRC liver metastases. The identification of liver-specific CAF gene expression profiles and unique ligand-receptor interactions provides new insights into metastatic mechanisms and potential therapeutic targets. Citation Format: Jongwon Lee, Yeseul Kim, Hyo Seon Ryu, Jongmin Sim, Chungyeul Kim, Hyun Woo Kwon, Hyun Je Kim, Jong Min Park, Ah-Reum Lim, Jung Sun Kim, Hwa Jung Sung, Xingyi Guo, Jungmin Choi, Jungyoon Choi. Mechanisms of metastasis revealed through single-cell spatial transcriptome analysis in patients with liver metastatic colorectal cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 5289.
Abstract 5269: CXCL10 promotes melanoma angiogenesis and tumor growth
Authors: Jong-Ho Lee
Journal: Cancer Research (2025)

Abstract Upregulation of CXC motif chemokine 10 (CXCL10) in melanoma patients has been found to be associated with melanoma progression. However, the role of endogenous CXCL10 from the host in melanoma tumor growth remains unclear. In the present study, we found that host-derived endogenous CXCL10 production was dramatically augmented during subcutaneous B16F10 melanoma tumor growth and that host ablation of CXCL10 in Cxcl10-/- mice showed a decrease in both angiogenesis and tumor growth of B16F10 melanoma in vivo. Several signaling pathways involved in production of pro-angiogenic factors and tumor growth were activated by CXCL10 in B16F10 melanoma cells. CXCL10 increased expression of pro-angiogenic factors, such as vascular endothelial growth factor (VEGF), platelet-derived growth factor subunit-B (PDGF-B), fibroblast growth factor 2 (FGF2), hepatocyte growth factor (HGF), and angiopoietin 2 (Angpt2), in B16F10 melanoma cells, resulting in enhanced tube formation and proliferation of human umbilical vein endothelial cells in vitro. In addition, CXCL10 directly enhanced B16F10 melanoma tumor growth in an in vitro three-dimensional cell culture system. Together, our findings reveal that amplified host-derived endogenous CXCL10 is critical for B16F10 melanoma angiogenesis and tumor growth. Therefore, CXCL10 might represent a therapeutic target for melanoma. Citation Format: Jong-Ho Lee. CXCL10 promotes melanoma angiogenesis and tumor growth [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 5269.