bims-mesote Biomed News
on Mesothelioma
Issue of 2022‒09‒18
three papers selected by
Laura Mannarino
Humanitas Research
  1. BMP and activin membrane-bound inhibitor regulate connective tissue growth factor controlling mesothelioma cell proliferation.
  2. Teserpaturev/G47Δ: First Approval.
  3. Combination of PD-1/PD-L1 checkpoint inhibition and dendritic cell therapy in mice models and in patients with mesothelioma.
  1. BMC Cancer. 2022 Sep 15. 22(1): 984
    BMP and activin membrane-bound inhibitor regulate connective tissue growth factor controlling mesothelioma cell proliferation.
    Nguyen Truong Duc Hoang, Ghmkin Hassan, Tomoya Suehiro, Yuichi Mine, Tohru Matsuki, Makiko Fujii.
      BACKGROUND: Malignant mesothelioma (MM) is an aggressive mesothelial cell cancer type linked mainly to asbestos inhalation. MM characterizes by rapid progression and resistance to standard therapeutic modalities such as surgery, chemotherapy, and radiotherapy. Our previous studies have suggested that tumor cell-derived connective tissue growth factor (CTGF) regulates the proliferation of MM cells as well as the tumor growth in mouse xenograft models.METHODS: In this study, we knock downed the bone morphogenetic protein and activin membrane-bound inhibitor (BAMBI) and CTGF in MM cells and investigated the relationship between both and their impact on the cell cycle and cell proliferation.
    RESULTS: The knockdown of CTGF or BAMBI reduced MM cell proliferation. In contrast to CTGF knockdown which decreased BAMBI, knockdown of BAMBI increased CTGF levels. Knockdown of either BAMBI or CTGF reduced expression of the cell cycle regulators; cyclin D3, cyclin-dependent kinase (CDK)2, and CDK4. Further, in silico analysis revealed that higher BAMBI expression was associated with shorter overall survival rates among MM patients.
    CONCLUSIONS: Our findings suggest that BAMBI is regulated by CTGF promoting mesothelioma growth by driving cell cycle progression. Therefore, the crosstalk between BAMBI and CTGF may be an effective therapeutic target for MM treatment.
    Keywords:  BAMBI; CTGF; Malignant mesothelioma; Proliferation; Cell cycle
    DOI:  https://doi.org/10.1186/s12885-022-10080-x
  2. BioDrugs. 2022 Sep 13.
    Teserpaturev/G47Δ: First Approval.
    James E Frampton.
      Teserpaturev/G47Δ (Delytact®) is a third-generation (triple-mutated) recombinant oncolytic herpes simplex virus type 1 being developed by Daiichi Sankyo Co., Ltd. for the treatment of certain solid cancers. Teserpaturev/G47Δ has been approved for the treatment of malignant glioma in Japan and is currently in clinical development for the treatment of prostate cancer (phase II), malignant pleural mesothelioma (phase I) and recurrent olfactory neuroblastoma (phase I). This article summarizes the milestones in the development of teserpaturev/G47Δ leading to this first approval for the treatment of malignant glioma.
    DOI:  https://doi.org/10.1007/s40259-022-00553-7
  3. Int J Cancer. 2022 Sep 14.
    Combination of PD-1/PD-L1 checkpoint inhibition and dendritic cell therapy in mice models and in patients with mesothelioma.
    Mandy van Gulijk, Bob Belderbos, Daphne Dumoulin, Robin Cornelissen, Koen Bezemer, Larissa Klaase, Floris Dammeijer, Joachim Aerts.
      Immunotherapy with anti-PD1/PD-L1 is effective in only a subgroup of patients with malignant pleural mesothelioma (MPM). We investigated the efficacy of a combination of anti-PD1/PD-L1 and dendritic cell (DC) therapy to optimally induce effective anti-tumor immunity in MPM in both humans and mice. Data of nine MPM patients treated with DC therapy and sequential anti-PD1 treatment were collected and analyzed for progression-free survival (PFS) and overall survival (OS). Survival and T-cell responses were monitored in AC29 mesothelioma-bearing mice treated concurrently with the combination therapy; additionally, the role of the tumor-draining lymph node (TDLN) was investigated. The combination therapy resulted in a median OS and PFS of 17.7 and 8.0 months, respectively. Grade 3-4 treatment-related adverse events had not been reported. Survival of the mesothelioma-bearing mice treated with the combination therapy was longer than that of untreated mice, and coincided with improved T-cell activation in peripheral blood and less T-cell exhaustion in end stage tumors. Comparable results were obtained when solely the TDLN was targeted. We concluded that this combination therapy is safe and shows promising OS and PFS. The murine data support that PD-L1 treatment may reinvigorate the T-cell responses induced by DC therapy, which may primarily be the result of TDLN targeting. This article is protected by copyright. All rights reserved.
    Keywords:  Dendritic cell therapy; anti-PD-L1; anti-PD1; checkpoint blockade; mesothelioma
    DOI:  https://doi.org/10.1002/ijc.34293
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