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    DRUG:

    ADP-A2M10

    i
    Other names: MAGE A10 TCR, MAGEA10 TCR, ADP-A2M10, Mage-A10 TCR, MAGEA10ᶜ⁷⁹⁶T, autologous genetically modified MAGE A10ᶜ⁷⁹⁶T cells, MAGE A10-specific T-cells, MAGE A10-transduced lymphocytes, MAGE-A10 SPEAR T-cell therapy
    Company:
    Adaptimmune
    Drug class:
    TCR modulator, MAGE-A10 inhibitor
    Related drugs:
    4ms
    Brief Communication on MAGE-A4 and Coexpression of Cancer Testis Antigens in Metastatic Synovial Sarcomas: Considerations for Development of Immunotherapeutics. (PubMed, J Immunother)
    Among MAGE-As, MAGE-A4 had the highest prevalence (65%), followed by MAGE-A10 (15%) and MAGE-A9 (13%)...Complementary immunohistochemical analyses were used to establish the positive correlation between RNA and protein expression for MAGE-A4 and NY-ESO-1. These data inform the strategy for optimal coverage of the SyS patient population with T-cell therapies, offering patients with SyS new options for single or combined second lines of treatment.
    Journal • IO biomarker • Metastases
    |
    CTAG1B (Cancer/testis antigen 1B) • MAGEA4 (Melanoma antigen family A, 4) • PRAME (Preferentially Expressed Antigen In Melanoma)
    |
    MAGEA4 expression
    |
    ADP-A2M10
    over2years
    Phase 1 Clinical Trial Evaluating the Safety and Anti-Tumor Activity of ADP-A2M10 SPEAR T-Cells in Patients With MAGE-A10+ Head and Neck, Melanoma, or Urothelial Tumors. (PubMed, Front Oncol)
    Patients underwent lymphodepletion with fludarabine and cyclophosphamide prior to receiving ADP-A2M10. Persistence of ADP-A2M10 in the peripheral blood and trafficking of ADP-A2M10 into the tumor was demonstrated. Because MAGE-A10 expression frequently overlaps with MAGE-A4 expression in tumors and responses were observed in the MAGE-A4 trial (NCT03132922), this clinical program closed, and trials with SPEAR T-cells targeting the MAGE-A4 antigen are ongoing.
    P1 data • Journal • IO biomarker
    |
    HLA-A (Major Histocompatibility Complex, Class I, A) • MAGEA4 (Melanoma antigen family A, 4)
    |
    HLA-A*02 • HLA-A2 positive • MAGEA4 expression
    |
    cyclophosphamide • fludarabine IV • ADP-A2M10
    over2years
    Phase I clinical trial evaluating the safety and efficacy of ADP-A2M10 SPEAR T cells in patients with MAGE-A10 advanced non-small cell lung cancer. (PubMed, J Immunother Cancer)
    ADP-A2M10 demonstrated an acceptable safety profile and no evidence of toxicity related to off-target binding or alloreactivity. There was persistence of ADP-A2M10 in peripheral blood as well as ADP-A2M10 trafficking into the tumor. Given the discovery that MAGE-A10 and MAGE-A4 expression frequently overlap, this clinical program closed as trials with SPEAR T cells targeting MAGE-A4 are ongoing.
    P1 data • Clinical Trial,Phase I • Journal • IO biomarker
    |
    HLA-A (Major Histocompatibility Complex, Class I, A) • MAGEA4 (Melanoma antigen family A, 4)
    |
    HLA-A*02 • HLA-A*02 + MAGEA10 expression • HLA-A2 positive • MAGEA4 expression
    |
    cyclophosphamide • fludarabine IV • ADP-A2M10
    almost3years
    Engineering Cancer Antigen-Specific T Cells to Overcome the Immunosuppressive Effects of TGF-β. (PubMed, J Immunol)
    We previously generated specific peptide enhanced affinity receptor TCRs recognizing the HLA-A*02-restricted peptides New York esophageal squamous cell carcinoma 1 (NY-ESO-1)/l-Ag family member-1A (TCR: GSK3377794, formerly NY-ESO-1) and melanoma Ag gene A10 (TCR: ADP-A2M10, formerly melanoma Ag gene A10). In this article, we show that exogenous TGF-β inhibited in vitro proliferation and effector functions of human T cells expressing these first-generation high-affinity TCRs, whereas inhibition was reduced or abolished in the case of second-generation TCRs coexpressed with dnTGFβRII (e.g., GSK3845097)...As an example, immunohistochemistry/RNAscope identified TGF-β-positive cells close to T cells in tumor nests and stroma, which had low frequencies of cells expressing IFN-γ in a non-small cell lung cancer setting. Coexpression of dnTGFβRII may therefore improve the efficacy of TCR-transduced T cells.
    Journal
    |
    HLA-A (Major Histocompatibility Complex, Class I, A) • IFNG (Interferon, gamma) • CTAG1B (Cancer/testis antigen 1B) • TGFB1 (Transforming Growth Factor Beta 1)
    |
    IFNG expression
    |
    ADP-A2M10 • letetresgene autoleucel (GSK3377794) • GSK3845097
    over3years
    MAGE A10ᶜ⁷⁹⁶T for Advanced NSCLC (clinicaltrials.gov)
    P1, N=28, Completed, Adaptimmune | Active, not recruiting --> Completed | Trial completion date: Dec 2034 --> Mar 2021
    Clinical • Trial completion • Trial completion date
    |
    EGFR (Epidermal growth factor receptor) • PD-L1 (Programmed death ligand 1) • ALK (Anaplastic lymphoma kinase) • ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS) • HLA-A (Major Histocompatibility Complex, Class I, A)
    |
    EGFR mutation • ALK rearrangement
    |
    ADP-A2M10