NY-ESO-1 combined with MPLA vaccine / National Institute of Science and Technology of Research in Immunology - LARVOL DELTA

Platinum Talen-Mediated Knock-in of Single-Stranded DNA Templates Facilitates Manufacturing of Clinical-Scale Non-Virally Gene-Edited T Cells from Peripheral Blood (ASH 2023) - "As a model TCR, we selected a 1G4 clone that reacts with NY-ESO-1-derived peptide in an HLA-A*02-restricted manner... We have successfully designed Platinum TALEN mRNA pairs targeting TRAC and TRBC which facilitate the production of genome-edited human primary T cells. We also developed an electroporation and expansion culture protocol that enables us to produce viable genome-edited 1G4-transduced T cells at a large cell dose equivalent to a clinical scale. Collectively, these results suggest that targeted orthotopic knock-in of antigen-specific TCR-encoding ssDNA into the TCR locus by the use of Platinum TALEN is a promising strategy that can be applied for the clinical manufacturing of therapeutic TCR-T cells."

Clinical • IO biomarker • Infectious Disease • CTAG1B • HAVCR2 • HLA-A • IL2 • PD-1

Ablation of Cullin-5 in Primary Human T Cells Improves Tumor Killing and Persistence in BCMA-Targeting CAR-T Cells in a Multiple Myeloma Model (ASH 2023) - "Primary T cells from two donors were transduced with lentivirus containing a NY-ESO-1 TCR as well as a genome-wide sgRNA library and subsequently CRISPR edited using Cas9-RNP electroporation...The template for the B Cell Maturation Antigen (BCMA)-specific CAR bb2121 was then delivered to the TRAC locus via CRISPR/Cas9-RNP and adeno-associated virus (AAV)...We found a significant advantage in tumor killing of CUL5 ablated T cells compared to control cells in this ex vivo setting, suggesting an improved functional persistence. In summary, our findings identify the CUL5 complex as a novel potential therapeutic target to improve T cell persistence and counteract T cell exhaustion in order to improve the efficacy of adaptive cell immunotherapies for the treatment of BCMA+ hematological malignancies."

CAR T-Cell Therapy • IO biomarker • Hematological Malignancies • Leukemia • Lymphoma • Melanoma • Multiple Myeloma • Oncology • Solid Tumor • CTAG1B • PRKDC • TNFA

Circular Rna Vaccine Synergizes With Anti-PD-1 to Augment Therapeutic Efficacy in Lung Cancer (IASLC-WCLC 2025) - "Methods : The circRNA vaccine encoding NY-ESO-1 (a highly immunogenic cancer-testis antigen) was synthesized using our proprietary circular RNA platform and encapsulated in lipid nanoparticles...The vaccine mediates TME remodeling by promoting inflammatory transformation. This study proposes a promising strategy for lung cancer patients."

Circular RNA • Clinical • Infectious Disease • Lung Cancer • Oncology • Solid Tumor • CD8 • CTAG1B

Immunotherapeutic targeting of NY-ESO-1 in malignant meningiomas with TCR-transduced T-cells. (PubMed, J Neurooncol) - "NY-ESO-1 TCR-T induces cytolysis in meningiomas in vitro, and its efficacy correlates with NY-ESO-1 expression. Systemic ACT results in significantly increased survival in vivo in high-grade meningioma. Therefore, targeting NY-ESO-1 may be a clinically feasible immunotherapeutic strategy for treating high-grade meningiomas."

IO biomarker • Journal • Brain Cancer • Meningioma • Oncology • Solid Tumor • CTAG1B

T cell engineering using V(D)J recombination allows tumor growth inhibition in mice (ASGCT 2025) - "Human cord blood or bone marrow derived HSPCs were grown on feeder cells with an SPEM-2 medium for 5 days and then transduced with a 7e5 vector genomes per cell of an AAV6 vector coding for either a CAR anti-CD19 or a TCR targeting an NY-ESO1 peptide presented on HLA-A*02... VDJ targeting produces potent naïve T cells that may be transplanted in lower numbers and have increased persistence compared to T cells engineered with state-of-the-art technologies. VDJ targeting is thus an efficient T cell engineering technology applicable in the autologous, allogeneic and in vivo engineering settings. Disease Focus of Abstract:Cancer Solid Tumors"

Preclinical • Hematological Malignancies • Melanoma • Oncology • Solid Tumor • CD19 • CTAG1B • FLT3 • HLA-A • IL7

Uncovering T-cell receptor clones and immunogenic targets in HER2DX-defined HER2-positive breast cancer (AACR 2025) - "53 of them (7%) recognized TAA, primarily MART1 (18.9%), followed by gp100, ABCD3, MAGEA6, KRAS, NY-ESO1, p53, TERT, and others... Early-stage HER2+ BC with high IGG expression is characterized by a robust, polyclonal immune response, with TCR clones targeting both tumor and viral antigens. These findings suggest enhanced immune fitness and may explain IGG favorable prognostic value. The discovery of shared TCR clones across tumors may help identify immunogenic targets, providing new opportunities for developing immune-based treatments or engineered T-cell therapies."

IO biomarker • Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Oncology • Solid Tumor • ABCD3 • CD27 • CD8 • CTAG1B • CTLA4 • GZMA • HER-2 • IFNG • KRAS • MAGEA6 • MLANA • PD-1 • PRF1

huHSC-NKG-ProF mouse model: a reliable tool for advancing tumor immunology research (SITC 2024) - "Treatment commenced when tumor volume reached 80–100 mm³, using either a tumor vaccine (QW × 3) or rituximab (5 mpk × 4)...In a study targeting the NY-ESO-1 mRNA tumor vaccine, we constructed huHSC-NKG-ProF mice using HLA-A2 matched HSC donors...(B) Efficacy study of ADCC research. (C) The Inflammatory Bowel Disease (IBD) phenotype after 3% DSS induction in huHSC-NKG-ProF mice"

Preclinical • Hematological Malignancies • Leukemia • Melanoma • Oncology • Solid Tumor • CTAG1B • IFNG

huHSC-NKG-ProF mouse model: a reliable tool for advancing tumor immunology research (SITC 2024) - "Treatment commenced when tumor volume reached 80–100 mm³, using either a tumor vaccine (QW × 3) or rituximab (5 mpk × 4)...In a study targeting the NY-ESO-1 mRNA tumor vaccine, we constructed huHSC-NKG-ProF mice using HLA-A2 matched HSC donors...(B) Efficacy study of ADCC research. (C) The Inflammatory Bowel Disease (IBD) phenotype after 3% DSS induction in huHSC-NKG-ProF mice"

Preclinical • Hematological Malignancies • Leukemia • Melanoma • Oncology • Solid Tumor • CTAG1B • IFNG

Development of tumor-restricted IL-12 with antigen-dependent expression and localized IL-12 activity (AACR 2024) - "Using Outpace's OutSmart™ technology, we designed a tumor-restricted IL-12 (trIL-12) that is under control of an activation-inducible promoter and auto-inactivates within minutes after secretion.T cells were engineered via lentiviral vectors (LVV) to express wild-type single-chain IL-12 (WT scIL-12) or trIL-12 under the control of an activation-inducible promoter; a second LVV introduces an NY-ESO-1 TCR...Unlike WT scIL-12, trIL-12 activity is localized to the region around the producing T cell and systemic IL-12 exposure is not observed in vivo. Collectively, these preclinical data suggest that trIL-12 may enable the development of potent T-cell therapeutics while maintaining an acceptable safety profile."

Oncology • CTAG1B • IFNG • IL12A

[VIRTUAL] CRISPR-Mediated Genome Editing to Redirect T Cells against Non-Small Cell Lung Cancer (ASGCT 2021) - "TCR-engineered T cells derived from HLA-A*0201-typed NSCLC patients co-cultured with patient-derived cancer cells expressing NY-ESO-1 and analysed by flow cytometry for their killing activity, demonstrated that TCR engineering enabled T cells to recognize and kill NSCLC cells. These data strongly encourage the application of CRISPR-mediated non-viral TCR editing to generate tumor-specific T cells able to kill NSCLC cells, contributing to the preclinical validation of adoptive T cell therapy with CRISPR-mediated engineered T cells for the treatment of lung cancer."

IO biomarker • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • CTAG1B

PeptiCRAd - a novel oncolytic virus based therapeutic cancer vaccine for the treatment of solid tumors (CIMT 2019) - "...PeptiCRAd targeted to NY-ESO-1 and MAGE-A3 proteins, or the same virus without peptides (OV) were given intratumorally (i.t.) on days 1, 2, 3 and 12...In summary, PeptiCRAd monotherapy was able to trigger a systemic CD8+ T-cell response and concomitant tumor growth inhibition in clinically relevant humanized mouse melanoma model. PeptiCRAd improved the tumor targeting specificity of OV and the data provides a strong rationale for checkpoint inhibitor combination."

Oncolytic Virus

PeptiCRAd - a novel oncolytic virus based therapeutic cancer vaccine for the treatment of solid tumors (CIMT 2019) - "...PeptiCRAd targeted to NY-ESO-1 and MAGE-A3 proteins, or the same virus without peptides (OV) were given intratumorally (i.t.) on days 1, 2, 3 and 12...In summary, PeptiCRAd monotherapy was able to trigger a systemic CD8+ T-cell response and concomitant tumor growth inhibition in clinically relevant humanized mouse melanoma model. PeptiCRAd improved the tumor targeting specificity of OV and the data provides a strong rationale for checkpoint inhibitor combination."

Oncolytic Virus