bims-myxlip Biomed News
on Myxoid liposarcoma
Issue of 2021‒07‒18
two papers selected by
Laura Mannarino
Humanitas Research

  1. J Clin Oncol. 2021 Jul 14. JCO2003452
      PURPOSE: CMB305 is a heterologous prime-boost vaccination regimen created to prime NY-ESO-1-specific CD8 T-cell populations and then activate the immune response with a potent TLR-4 agonist. This open-label randomized phase II trial was designed to investigate the efficacy and safety of adding the CMB305 regimen to atezolizumab (anti-programmed death ligand-1 therapy) in comparison with atezolizumab alone in patients with synovial sarcoma or myxoid liposarcoma.PATIENTS AND METHODS: Patients with locally advanced, relapsed, or metastatic synovial sarcoma or myxoid liposarcoma (any grade) were randomly assigned to receive CMB305 with atezolizumab (experimental arm) or atezolizumab alone (control arm). The primary end points were progression-free survival (PFS) and overall survival (OS) analyzed using the Kaplan-Meier method. Safety and immune responses were assessed.
    RESULTS: A total of 89 patients were enrolled; 55.1% had received ≥ 2 prior lines of chemotherapy. Median PFS was 2.6 months and 1.6 months in the combination and control arms, respectively (hazard ratio, 0.9; 95% CI, 0.6 to 1.3). Median OS was 18 months in both treatment arms. Patients treated with combination therapy had a significantly higher rate of treatment-induced NY-ESO-1-specific T cells (P = .01) and NY-ESO-1-specific antibody responses (P < .0001). In a post hoc analysis of all dosed patients, OS was longer (36 months) in the subset who developed anti-NY-ESO-1 T-cell immune response (hazard ratio, 0.3; P = .02).
    CONCLUSION: Although the combination of CMB305 and atezolizumab did not result in significant increases in PFS or OS compared with atezolizumab alone, some patients demonstrated evidence of an anti-NY-ESO-1 immune response and appeared to fare better by imaging than those without such an immune response. Combining prime-boost vaccines such as CMB305 with anti-programmed death ligand-1 therapies merits further evaluation in other clinical contexts.
  2. Pathol Int. 2021 Jul 15.
      Disease-specific gene fusions are reportedly major driver mutations in approximately 30% of bone and soft tissue sarcomas. Most fusion genes encode transcription factors or co-factors that regulate downstream target genes, altering cell growth, lineage commitment, and differentiation. Given the limitations of investigating their functions in vitro, the generation of mouse models expressing fusion genes in the appropriate cellular lineages is pivotal. Therefore, we generated a series of mouse models by introducing fusion genes into embryonic mesenchymal progenitors. This review describes mouse models of Ewing, synovial, alveolar soft part, and CIC-rearranged sarcomas. Furthermore, we describe the similarities between these models and their human counterparts. These models provide remarkable advantages to identify cells-of-origin, specific collaborators of fusion genes, angiogenesis key factors, or diagnostic biomarkers. Finally, we discuss the relationship between fusion proteins and the epigenetic background as well as the possible role of the super-enhancers.
    Keywords:  CIC-rearranged sarcoma; Ewing sarcoma; alveolar soft part sarcoma; angiogenesis; cell-of-origin; fusion gene; mouse model; super-enhancer; synovial sarcoma