ABIO-0501 / Abiogen - LARVOL DELTA

Establishing a multi-modal, cell therapy characterization workflow to identify cell subsets with heightened cytotoxicity (AACR 2025) - P1 | "We leveraged TALL-104 cells before validating compatibility with clinical-stage cell therapies with AIC100 - a Phase 1 CAR-T product targeting thyroid cancer (NCT04420754). We are continuing to identify the optimal CD4:CD8 compositions for greater potency. We envision multi-modal characterization of clinical products with our platform, pre and post-patient infusion, will inform efforts to advance cell therapies for solid tumors."

IO biomarker • B Cell Lymphoma • Endocrine Cancer • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Solid Tumor • Thyroid Gland Carcinoma • CD4 • CD8 • LAMP2

Intracellular and extracellular biochemical functions of V-domain Ig-containing suppressor of T cell activation are regulated by crucial factors of tumour microenvironment (ITOC 2025) - "Materials and Methods We used human cancer and non-cancerous human cell lines including LN-18 glioblastoma cells, Calu6 lung cancer cells, PANC-1 pancreatic ductal adenocarcinoma cells, HuH7 hepatocellular carcinoma cells, BEAS-2B bronchial epithelial cells, THP-1 human acute myeloid leukaemia monocytes, Jurkat T cells, TALL-104 cytotoxic T cells and primary human CD3-positive T cells...Conclusions This work highlighted that some cancers (e. g. breast carcinoma, pancreatic ductal adenocarcinoma, pulmonary carcinoma) VISTA plays the role of immune checkpoint protein, while in other cancers (e. g. hepatocellular carcinoma, various colorectal cancers VISTA is mainly engaged in intracellular biochemical functions associated). These results indicate importance of understanding of differential functions of VISTA for development of personalised immunotherapies of cancer."

IO biomarker • Tumor microenvironment • Acute Myelogenous Leukemia • Brain Cancer • Breast Cancer • CNS Tumor • Colorectal Cancer • Glioblastoma • Hematological Malignancies • Hepatocellular Cancer • Leukemia • Lung Cancer • Oncology • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma • Solid Tumor • HAVCR2 • HIF1A • LGALS9 • SMAD3 • TGFB1 • VSIR

Multiplexed Cytokine Assessment of T- and NK-Cell Responses to Tumor Cells: Parallel Assessment of Biomarkers Associated with Efficacy, Safety, and Persistence (ASH 2024) - "Multiple CAR T therapies (eg Kymriah, Yescarta, and Breyanzi) have been approved by the FDA since 2017...Secreted biomarkers associated with efficacy and persistence (e.g. IFNγ, Granzyme B, IL7, IL15) were also detected in co-cultures of HEK293 with TALL104 further indicating that the TALL104 cell is facilitating a cytolytic mechanism and persisting due to T cell receptor / HLA engagement with target HEK293 cells...Here, we have demonstrated the utility of Meso Scale's multiplexed panels against relevant tool IECs and tumor cell co-culture models. The adaptation of these biomarker assays from in vitro screens may aid the development of new allogeneic cellular immunotherapies with improved outcomes."

Biomarker • Clinical • IO biomarker • Tumor cell • Brain Cancer • CNS Tumor • Glioma • Hematological Disorders • Hematological Malignancies • Oncology • Solid Tumor • CASP3 • CD40LG • GZMB • IFNG • IL10 • IL15 • IL18 • IL1B • IL2 • IL6 • IL7

Understanding Chitinase-3-like-1's role in chordoma immune evasion: implications for immunotherapy strategies (EORTC-NCI-AACR 2024) - "Our initial findings from protein and RNA suggest elevated Chi3l1 expression in JHC7 cells compared to U-CH1-N cells, offering a foundation for pursuing future experiments in this direction. Preliminary immunofluorescence similarly supports the production of Chi3l1 by chordoma cells. Conclusions & Future Directions: Differential Chi3l1 expression between the presumed precursor cell (notochordal U-CH1-N) and primary tumor cell (JHC7) demonstrates a possible target for chordoma EMT."

IO biomarker • Chordoma • Oncology • CD8 • CHI3L1 • PD-1 • PD-L1

ITGB6 as an inhibitor of T-cell killing via modulation of paracrine TGFβ signaling in pancreatic ductal adenocarcinoma. (ASCO 2024) - "Both KD and control shRNA cell lines were induced with doxycycline and subsequently co-cultured with TALL-104 T-cells. Survival data that clearly demonstrates the poor prognosis of ITGB6 expression, as well as the presently proposed mechanism of immunosuppression, provide ample justification for deploying anti-ITGB6 combination therapies to in vivo studies that facilitate translation of our findings into therapeutic clinical trials."

IO biomarker • Gastrointestinal Cancer • Oncology • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma • ITGB6 • SMAD4 • TGFB1

Integrin ɑvβ6 upregulation as a mechanism of T-cell evasion in head and neck squamous cell carcinoma (AACR 2024) - "The immune checkpoint inhibitor pembrolizumab (αPD-1) has been approved for recurrent or metastatic HNSCC and as a frontline therapy for unresectable disease...Both knockdown and control shRNA cell lines were pretreated with 1 μg/mL of doxycycline for five days to induce the shRNA and subsequently co-cultured with TALL-104 T-cells...To determine whether the T cell evasive effect of αvβ6 is driven by other immune checkpoints on the cancer cells or by the direct effect that TGFβ has on immune cells, we show the generation of relevant mouse αvβ6 shRNA knockdown cells. These syngeneic in vivo studies will facilitate cytokine profiling to uncover the dynamics of tumor-immune cell interactions in response to αvβ6 inhibition."

IO biomarker • Head and Neck Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • ITGB6 • PD-L1 • TGFB1

IL-6-Derived Autocrine Lactate Promotes Immune Escape of Uveal Melanoma. (PubMed, Invest Ophthalmol Vis Sci) - "TALL-104 and NK-92MI-mediated cell killing assays were used to examine the immune resistance of UM cells...Notably, lactate secreted by IL-6-treated UM cells was crucial in influencing PD-L1 and HLA-E stability via the GPR81-cAMP-PKA signaling pathway. Our data reveal a novel mechanism by which UM cells acquire an immune-escape phenotype by metabolic reprogramming and reinforce the importance of the link between inflammation and immune escape."

IO biomarker • Journal • Eye Cancer • Melanoma • Oncology • Solid Tumor • Uveal Melanoma • HLA-E • IL6 • LDHA • PD-L1 • PFKP

Intracellular and extracellular biochemical activities of V-domain Ig-containing suppressor of T cell activation or VISTA (ITOC 2024) - "Materials and Methods We used human cancer and non-cancerous cell lines including LN-18 glioblastoma cells, BEAS-2B bronchial epithelial cells, THP-1 human acute myeloid leukaemia monocytes, Jurkat T cells, TALL-104 cytotoxic T cells and primary human CD3-positive T cells...The immune checkpoint protein VISTA is a multifunctional component of cancer immune evasion machinery and T cell suppression displaying both ligand and receptor properties on the extracellular/inter-cellular levels. In addition, VISTA can be involved in intracellular signalling networks."

Acute Myelogenous Leukemia • Brain Cancer • CNS Tumor • Glioblastoma • Hematological Malignancies • Leukemia • Oncology • Solid Tumor • AMPK • BCL2L1 • GZMB • IL2 • LGALS9

Cytotoxic immune cells do not affect TDP-43 and p62 sarcoplasmic aggregation but influence TDP-43 localisation. (PubMed, Sci Rep) - "In an in vitro setting, cytotoxic immune cells did not cause TDP-43 or p62 sarcoplasmic aggregation, suggesting cellular cytotoxicity may not trigger aggregation of these proteins. However TALL-104 coculture influenced TDP-43 localisation, suggesting cytotoxic immune cells may contribute to TDP-43 localisation shifts which is observed in sIBM."

Immune cell • Journal • Immunology • Inflammation • Myositis • CD8 • IFNG • TARDBP • TNFA

Vascular Immune Evasion of Mesenchymal Glioblastoma Is Mediated by Interaction and Regulation of VE-Cadherin on PD-L1. (PubMed, Cancers (Basel)) - "Knockdown of VE-cad or the PD-L1 gene ablated the effects of YKL-40 and reinvigorated TALL-104 cell immunity against vessels. In summary, our study demonstrates a novel vascular immune escape mechanism by which mGBM promotes tumor vascularization and malignant transformation."

IO biomarker • Journal • Brain Cancer • CNS Tumor • Glioblastoma • Glioma • Oncology • Solid Tumor • Transplantation • CD8 • CDH5 • CHI3L1 • CTNNB1 • PD-1 • PD-L1 • VIM

Pan-integrin inhibitor GLPG-0187 promotes T-cell killing of mismatch repair-deficient colorectal cancer cells by suppression of SMAD/TGF-β signaling. (PubMed, Am J Cancer Res) - "GLPG-0187 promoted significant immune cell killing of the CRC cells by TALL-104 T lymphoblast cells and reduced phosphoSMAD2 in HCT116 p53-null cells either in the absence or presence of exogenous TGF-β. Our results suggest that TGF-β signaling inhibition by a general integrin receptor inhibitor may boost T-cell killing of MMR-deficient colorectal cancer cells and suggest that a combination of anti-GDF-15 in combination with TGF-β blockade be further investigated in the treatment of MMR-deficient mCRC. Our results support the development of a novel immune-based therapeutic strategy to treat colorectal cancer by targeting the TGF-β signaling pathway through integrin receptor blockade."

Journal • Mismatch repair • Colorectal Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor • CCL20 • CXCL5 • GDF15 • TGFB1

Broad spectrum integrin inhibitor GLPG-0187 bypasses immune evasion in colorectal cancer by TGF-β signaling mediated downregulation of PD-L1. (PubMed, Am J Cancer Res) - "Fluorescently labeled wild-type HCT-116 colorectal cancer cells and TALL-104 T-cells were co-cultured and treated with GLPG-0187, a small molecule integrin inhibitor, at various doses. Probing for additional downstream markers of TGF-β and up-stream markers of PD-L1 will help to further elucidate this mechanism. Further co-culture experiments will also include anti-PD-L1 and anti-PD-1 therapy to investigate the viability of integrin inhibition as an adjuvant to immune checkpoint blockade."

IO biomarker • Journal • Colorectal Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor • PD-L1 • TGFB1

Bypassing immune evasion in colorectal cancer by integrin inhibition-mediated downregulation of PD-L1 (AACR 2023) - "Fluorescently labeled wild-type HCT-116 colorectal cancer cells and TALL-104 T-cells were co-cultured and treated with GLPG0187, a small molecule integrin inhibitor, at various doses. Probing for additional downstream markers of TGFβ and up-stream markers of PD-L1 will help to further elucidate the mechanism. Further co-culture experiments include anti-PD-L1 and anti-PD-1 therapy to investigate the viability of integrin inhibition as an adjuvant to immune checkpoint blockade."

IO biomarker • Colorectal Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor

Combination treatment with pH modulating drugs and immune checkpoint inhibitors increases TALL-104 cytotoxicity in preclinical co-culture experiments (AACR 2023) - "Phase 1 clinical trials are ongoing for treatment of primary liver cancer and uveal melanoma with liver metastases using pressure-enabled drug delivery of SD-101 in combination with systemic immune checkpoint inhibitors (ICIs). Combination PMD and ICI studies are needed to inform drug combinations and dosages in syngeneic murine models of primary liver cancer and CRCLM. Subcutaneous and orthotopic tumor models are expected to demonstrate the efficacy of local PMD treatment with systemic immunotherapy."

Checkpoint inhibition • Preclinical • Colorectal Cancer • Eye Cancer • Gastrointestinal Cancer • Hepatocellular Cancer • Liver Cancer • Melanoma • Oncology • Solid Tumor • Uveal Melanoma • B2M • CXCL10 • CXCL5 • CXCL8 • GDF15

Combination of palbociclib, a potent CDK4/6 inhibitor, with anti-PD1 drug pembrolizumab treatment to promote T-cell mediated glioblastoma tumor cell death under hypoxia (AACR 2023) - "The standard treatment options are surgery, radiation therapy, and chemotherapy using temozolomide. Immune cell co-culture, comprising of GBM cell lines plus TALL104 human leukemia T cells, was used to determine the amount of tumor cell death with palbociclib, pembrolizumab and a combination at different time points in both normoxia and hypoxia conditions. Our results are providing insights into improving immune checkpoint therapy for GBM patients."

Tumor cell • Brain Cancer • CNS Tumor • Glioblastoma • Hematological Malignancies • Leukemia • Oncology • Solid Tumor • CD4 • HIF1A

The immunostimulatory effect of 9-ING-41, a small molecule GSK-3 inhibitor, in sarcomas (AACR 2023) - "Additionally, both cancer cell lines as well as TALL-104 T-cells and NK-92 NK cells were treated with 0.5 μM 9-ING-41 for 24 hours and harvested for Luminex cytokine profiling. The treatment cohorts for these experiments include 9-ING-41 combined with either anti-PD-L1, anti-PD-1, or anti-CTLA-4 immune checkpoint inhibitors. Our results suggest a promising combination therapeutic strategy for patients with soft tissue and bone sarcomas and future work will strive to better elucidate the mechanisms of efficacy."

IO biomarker • Liposarcoma • Oncology • Osteosarcoma • Sarcoma • Solid Tumor • CXCL11 • CXCL8 • IFNG • IL18 • IL6 • TNFSF10

Classical chemotherapy modulates cytokine secretion in the MSS CRC immune microenvironment and enhances T cell killing (AACR 2023) - "Most patients receive chemotherapies 5-FU and folinic acid combined with oxaliplatin, irinotecan, or both...5-FU + folinic acid + oxaliplatin -/+ pembrolizumab enhances TALL-104-mediated killing of SW480 and HT29 cells...Chemotherapy pre-treatment may enhance TALL-104 cell infiltration in MSI tumors. Future directions include evaluation of concurrent vs. sequential chemotherapy + immunotherapy regimens using murine models of MSS colorectal cancer and isolation of circulating tumor cells from patients before and after chemotherapy treatment to measure effects on cytokine secretion and immune cell killing."

Colorectal Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor • B2M • CCL2 • CCL3 • CHI3L1 • CSF2 • CTCs • FASLG • IFNG • IL10 • IL6 • MSI

Temozolomide combined with ipilimumab + nivolumab enhances T cell killing of MGMT-expressing, MSS colorectal cancer cells (AACR 2023) - "CRC and GBM cells were co-cultured with TALL-104 cells -/+ TMZ and -/+ ICI to measure TALL-104-mediated cell death. Our results indicate that TMZ sensitizes MSS, MGMT-expressing CRC cells to ipilimumab + nivolumab ICI. Importantly, this suggests that TMZ-mediated sensitization to ipilimumab + nivolumab is independent of MGMT status and the patient cohort that may benefit TMZ + ipilimumab + nivolumab may be expanded to CRC patients with MGMT-expressing, MSS tumors."

IO biomarker • Brain Cancer • CNS Tumor • Colorectal Cancer • Gastrointestinal Cancer • Glioblastoma • Oncology • Solid Tumor • MGMT

Integrin inhibitor GLPG-0187 promotes T-cell killing of mismatch repair-deficient colorectal cancer cells by suppression of SMAD/TGF-β signaling (AACR 2023) - "However, GLPG-0187 promoted significant immune cell killing of the CRC cells by TALL-104 T lymphoblast cells. Our results suggest that TGF- signaling inhibition by a general integrin receptor inhibitor may boost T-cell killing of MMR-deficient colorectal cancer cells, and suggest that a combination of anti-GDF-15 in combination with TGF- β blockade should be further investigated in the treatment of MMR-deficient mCRC. Our results support the development of a novel immune-based therapeutic strategy to treat colorectal cancer by targeting the TGF-β signaling pathway through integrin receptor blockade."

Mismatch repair • Colorectal Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor • CCL20 • CXCL5 • GDF15 • TGFB1

Construction and stable gene expression of AGR2xPD1 bi-specific antibody that enhances attachment between T-Cells and lung tumor cells, suppress tumor cell migration and promoting CD8 expression in cytotoxic T-cells. (PubMed, Saudi Pharm J) - "Applying this BsAb in a T cell-Tumor cell co-culture system showed that targeting both PD1 and AGR2 with this BsAb induces the attachment of TALL-104 (CD8 T-lymphocytes) cells onto co-cultured H460 AGR2 Lung tumor cells and significantly reduces migration of H460 cells...These effects are significantly reduced with AGR2 expression negative WI38 cells. Our results demonstrate that the AGR2xPD1 BsAb could be a potential therapeutic agent to provide better solid tumor targeting and synergetic efficacy for treating AGR2+ cancer by blocking AGR2 paracrine signaling to reduce tumor survival, and redirecting cytotoxic T-cells into AGR2+ cancer cells."

IO biomarker • Journal • Tumor cell • Immune Modulation • Inflammation • Lung Cancer • Oncology • Solid Tumor • AGR2 • CD8 • IFNG

2'-Hydroxy-4',5'-dimethoxyacetophenone Exhibit Collagenase, Aldose Reductase Inhibition, and Anticancer Activity Against Human Leukemic Cells: An In Vitro, and In Silico Study. (PubMed, Mol Biotechnol) - "MTT assay was also conducted to investigate the anti-leukemic effect of 2'-Hydroxy-4',5'-dimethoxyacetophenone on human acute leukemia cells (32D-FLT3-ITD, Human HL-60/vcr, MOLT-3, and TALL-104 cell lines) and DPPH assay for establishing activity against oxidative stress...In DPPH free radical scavenging assay, 2'-Hydroxy-4',5'-dimethoxyacetophenone showed strong inhibitory activity with IC of 157 µg/mL, which found comparable to the standard BHT. Our study demonstrated prominent pharmacological benefit of 2'-Hydroxy-4',5'-dimethoxyacetophenone, against various leukemic cell lines, aldose reductase and collagenase enzymes, and free radical scavenging activity."

Journal • Preclinical • Diabetes • Hematological Disorders • Hematological Malignancies • Leukemia • Metabolic Disorders • Oncology • AKR1B1

Preventing cystatin F proteolytic activation by cathepsin V increases cytotoxicity of effector immune cells (AACR-NCI-EORTC 2022) - "In the lysosomes, cystatin F is activated from inactive dimeric form to active monomer by cathepsin V, which cleaves 15 N-terminal amino acids from cystatin F. As increased levels of cystatin F may contribute to the immunosuppressive status of the tumor microenvironment, we evaluated the effects of cathepsin V inhibition on the cytotoxicity of immune effector cells NK-92 and TALL-104.Materials and Molecular docking was used to evaluate interactions of small molecular compounds from commercial libraries with cathepsin V. A set of selected compounds was evaluated by enzyme kinetics for the enzyme inhibition, selectivity and reversibility of binding... Selective inhibition of cathepsin V prevents the monomerization and activation of cystatin F. By targeting of cystatin F activating peptidase, we can reduce the detrimental effects of cystatin F on cytotoxic cells in the tumor microenvironment. No"

Oncology • CTSS

Cathepsin V inhibition prevents the activation of cystatin F and increases immune cell cytotoxicity (ITOC 2022) - "We evaluated the effects of cathepsin V inhibition on the cytotoxicity of immune effector cells NK-92 and TALL-104...As expected, treatment of immune effector cells with E-64d decreased cytotoxic function, as this inhibitor impairs the activities of all cathepsins including cathepsins C, H, and L. However, treatment of cytotoxic cells with cathepsin V inhibitor increased their cytotoxicity. Conclusions Selective inhibition of cathepsin V prevents the monomerization and activation of cystatin F. By targeting the activating protease of cystatin F, we can reduce the detrimental effects of cystatin F on cytotoxic cells in the tumor microenvironment."

Oncology • CTSS

Galectin 9 dependent immune evasion machinery as a potential target for personalised immunotherapy of cancer (ITOC 2022) - "Jurkat T lymphocytes, TALL-104 cytotoxic T cells and primary human and mouse CD3-positive T lymphocytes were employed for immune evasion studies...As such, personalised targeted immunotherapy could be adapted. Further investigations required to map the immune evasion machinery for each type of cancer and design the best targets for personalised immunotherapy of human malignancies."

IO biomarker • Brain Cancer • Breast Cancer • CNS Tumor • Glioblastoma • Kidney Cancer • Oncology • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma • Renal Cell Carcinoma • Solid Tumor • HAVCR2 • LGALS9 • PD-1 • PD-L1 • SMAD3 • TGFB1

Selective induction of cell death in Jurkat cells with recombinant fungal lectin CNL (ITOC 2022) - "Remarkably, a plant lectin, Wisteria floribunda agglutinin (WFA), which shows similar specificity in ligand binding, showed less selective cytotoxicity and induced cell death in Jurkat cells, Tall-104 acute lymphoblastic leukemia, and Hut-87 cutaneous T-cell lymphoma cell lines with similar uncharacteristic features. Conclusions Selective targeting of Jurkat T cells may reflect potential applicability of CNL in novel strategies for treating and/or detecting acute T cell leukemia. The fungal Clitocybe nebularis lectin binds distinct cell surface glycoprotein receptors to induce cell death selectively in Jurkat cells."

Acute Lymphocytic Leukemia • Cutaneous T-cell Lymphoma • Hematological Malignancies • Leukemia • Lymphoma • Oncology • T Acute Lymphoblastic Leukemia • T Cell Non-Hodgkin Lymphoma • HMGB1 • PTPRC • SPN