Journal of Hematology & Oncology

Our medical research library holds 6 studies published in Journal of Hematology & Oncology (2014–2025). Each entry links to the study's record on PubMed and, where there is one, to the publisher's page and a free full text. 6 have an abstract, the authors' own summary as PubMed records it: open "Abstract" to read it.

About the journal

• Publisher: Biomed Central
• Published: 2008 to the present, England
• Language: English
• ISSN: 1756-8722 (electronic)
• Its record in the NLM Catalog

2020s

• WT1-mRNA dendritic cell vaccination of patients with glioblastoma multiforme, malignant pleural mesothelioma, metastatic breast cancer, and other solid tumors: type 1 T-lymphocyte responses are associated with clinical outcome. Z.N. Berneman, M. De Laere, P. Germonpré, et al. 2025;18(1):9. Letter PubMed · Publisher · Free full text

  Abstract

  Cell therapies, including tumor antigen-loaded dendritic cells used as therapeutic cancer vaccines, offer treatment options for patients with malignancies. We evaluated the feasibility, safety, immunogenicity, and clinical activity of adjuvant vaccination with Wilms' tumor protein (WT1) mRNA-electroporated autologous dendritic cells (WT1-mRNA/DC) in a single-arm phase I/II clinical study of patients with advanced solid tumors receiving standard therapy. Disease status and immune reactivity were evaluated after 8 weeks and 6 months. WT1-mRNA/DC vaccination was feasible in all patients, except one. Vaccination was well tolerated without evidence of systemic toxicity. The disease control rate and overall response rate among a total of 39 evaluable patients were 74.4% and 12.8%, respectively. Median overall survival (OS) was 43.7 months among 13 patients with glioblastoma multiforme, 41.9 months among 12 patients with metastatic breast cancer, and 48.8 months among 10 patients with malignant pleural mesothelioma, comparing favourably with historical controls reported in the literature. OS was longer in patients with stable disease at 8 weeks and disease control at 6 months versus patients without disease control at either time point. Disease control and higher OS were associated with antigen-specific type 1 CD4+ and/or CD8+ T-lymphocyte responses, mainly induced by WT1-mRNA/DC vaccination. Antigen-nonspecific type 2 CD8+ T-cell responses were common before WT1-mRNA/DC vaccination but did not show any association with clinical outcome. Collectively, these data indicate that WT1-mRNA/DC vaccination is feasible, safe, and immunogenic and shows clinical activity in patients with advanced solid tumors, suggesting that it has the potential to help improve their survival.

  © 2025. The Author(s).

2010s

• Mesothelin is a target of chimeric antigen receptor T cells for treating gastric cancer. J. Lv, R. Zhao, D. Wu, et al. 2019;12(1):18. PubMed · Publisher · Free full text

  Abstract

  Background: Gastric cancer (GC) is a common cancer in Asia and currently lacks a targeted therapy approach. Mesothelin (MSLN) has been reported to be expressed in GC tissue and could be targeted by chimeric antigen receptor (CAR) T cells. Mesothelin targeting CAR-T has been reported in mesothelioma, lung cancer, breast cancer, and pancreas cancer. However, the feasibility of using anti-MSLN CAR T cells to treat GC remains to be studied.

  Methods: We verified MSLN expression in primary human GC tissues and GC cell lines and then redirected T cells with a CAR containing the MSLN scFv (single-chain variable fragment), CD3ζ, CD28, and DAP10 intracellular signaling domain (M28z10) to target MSLN. We evaluated the function of these CAR T cells in vitro in terms of cytotoxicity, cytokine secretion, and surface phenotype changes when they encountered MSLN+ GC cells. We also established four different xenograft GC mouse models to assess in vivo antitumor activity.

  Results: M28z10 T cells exhibited strong cytotoxicity and cytokine-secreting ability against GC cells in vitro. In addition, cell surface phenotyping suggested significant activation of M28z10 T cells upon target cell stimulation. M28z10 T cells induced GC regression in different xenograft mouse models and prolonged the survival of these mice compared with GFP-transduced T cells in the intraperitoneal and pulmonary metastatic GC models. Importantly, peritumoral delivery strategy can lead to improved CAR-T cells infiltration into tumor tissue and significantly suppress the growth of GC in a subcutaneous GC model.

  Conclusion: These results demonstrate that M28z10 T cells possess strong antitumor activity and represent a promising therapeutic approach to GC.

• Antitumor activity of miR-34a in peritoneal mesothelioma relies on c-MET and AXL inhibition: persistent activation of ERK and AKT signaling as a possible cytoprotective mechanism. R. El Bezawy, M. De Cesare, M. Pennati, et al. 2017;10(1):19. PubMed · Publisher · Free full text

  Abstract

  Background: The value of microRNAs (miRNAs) as novel targets for cancer therapy is now widely recognized. However, no information is currently available on the expression/functional role of miRNAs in diffuse malignant peritoneal mesothelioma (DMPM), a rapidly lethal disease, poorly responsive to conventional treatments, for which the development of new therapeutic strategies is urgently needed. Here, we evaluated the expression and biological effects of miR-34a-one of the most widely deregulated miRNAs in cancer and for which a lipid-formulated mimic is already clinically available-in a large cohort of DMPM clinical samples and a unique collection of in house-developed preclinical models, with the aim to assess the potential of a miR-34a-based approach for disease treatment.

  Methods: miR-34a expression was determined by qRT-PCR in 45 DMPM and 7 normal peritoneum specimens as well as in 5 DMPM cell lines. Following transfection with miR-34a mimic, the effects on DMPM cell phenotype, in terms of proliferative potential, apoptotic rate, invasion ability, and cell cycle distribution, were assessed. In addition, three subcutaneous and orthotopic DMPM xenograft models were used to examine the effect of miR-34a on tumorigenicity. The expression of miRNA targets and the activation status of relevant pathways were investigated by western blot.

  Results: miR-34a was found to be down-regulated in DMPM clinical specimens and cell lines compared to normal peritoneal samples. miR-34a reconstitution in DMPM cells significantly inhibited proliferation and tumorigenicity, induced an apoptotic response, and declined invasion ability, mainly through the down-regulation of c-MET and AXL and the interference with the activation of downstream signaling. Interestingly, a persistent activation of ERK1/2 and AKT in miR-34a-reconstituted cells was found to counteract the antiproliferative and proapoptotic effects of miRNA, yet not affecting its anti-invasive activity.

  Conclusions: Our preclinical data showing impressive inhibitory effects induced by miR-34a on DMPM cell proliferation, invasion, and growth in immunodeficient mice strongly suggest the potential clinical utility of a miR-34a-replacement therapy for the treatment of such a still incurable disease. On the other hand, we provide the first evidence of a potential cytoprotective/resistance mechanism that may arise towards miRNA-based therapies through the persistent activation of RTK downstream signaling.

• miR-380-5p-mediated repression of TEP1 and TSPYL5 interferes with telomerase activity and favours the emergence of an "ALT-like" phenotype in diffuse malignant peritoneal mesothelioma cells. G. Cimino-Reale, P. Gandellini, F. Santambrogio, et al. 2017;10(1):140. PubMed · Publisher · Free full text

  Abstract

  Background: Understanding the molecular/cellular underpinnings of diffuse malignant peritoneal mesothelioma (DMPM), a fatal malignancy with limited therapeutic options, is of utmost importance for the fruitful management of the disease. In this context, we previously found that telomerase activity (TA), which accounts for the limitless proliferative potential of cancer cells, is prognostic for disease relapse and cancer-related death in DMPM patients. Consequently, the identification of factors involved in telomerase activation/regulation may pave the way towards the development of novel therapeutic interventions for the disease. Here, the capability of miR-380-5p, a microRNA negligibly expressed in telomerase-positive DMPM clinical specimens, to interfere with telomerase-mediated telomere maintenance and, hence, with cancer cell growth was assessed on preclinical models of DMPM.

  Methods: DMPM cells were transfected with a miR-380-5p synthetic precursor, and the effects of miRNA replacement were evaluated in terms of growing capability, induction of apoptosis and interference with TA. Reiterated weekly transfections were also performed in order to analyse the phenotype arising upon prolonged miR-380-5p reconstitution in DMPM cells.

  Results: The ectopic expression of miR-380-5p elicited a remarkable inhibition of TA and resulted in DMPM cell growth impairment and apoptosis induction. In particular, we demonstrated for the first time that these effects were the result of a molecular circuitry converging on telomerase associated protein 1 (TEP1), where the miRNA was able to target the gene both directly in unconventional targeting modality and indirectly via p53 accumulation consequent to miRNA-mediated downregulation of testis-specific protein, Y-encoded-like 5 gene. Moreover, miR-380-5p did not cause telomere attrition and cell growth arrest in long-term DMPM transfectants, which in turn showed slightly elongated telomeres and molecular features (e.g. c-circle DNA and reduced expression levels of chromatin remodeler ATRX) resembling an alternative lengthening of telomeres (ALT) phenotype.

  Conclusions: miR-380-5p interferes with TA in DMPM cells by targeting TEP1. Notably, in the long-term setting, miR-380-5p-mediated impairment of TA did not result in telomere attrition. Instead, a phenotype reminiscent of ALT emerged in DMPM cells as possible compensatory pathway that safeguards DMPM cell growth, an event that may be regarded as a potential resistance mechanism to anticancer therapies based on telomerase inhibitors.

• The next generation of immunotherapy: keeping lung cancer in check. A. Somasundaram, T.F. Burns. 2017;10(1):87. Review PubMed · Publisher · Free full text

  Abstract

  Lung cancer is the deadliest malignancy with more cancer deaths per year than the next three cancers combined. Despite remarkable advances in targeted therapy, advanced lung cancer patients have not experienced a significant improvement in mortality. Lung cancer has been shown to be immunogenic and responsive to checkpoint blockade therapy. Checkpoint signals such as CTLA-4 and PD-1/PD-L1 dampen T cell activation and allow tumors to escape the adaptive immune response. Response rates in patients with pretreated, advanced NSCLC were much higher and more durable with PD-1 blockade therapy compared to standard-of-care, cytotoxic chemotherapy. Therefore, PD-1 inhibitors such as nivolumab and pembrolizumab were rapidly approved for both squamous and nonsquamous lung cancer in the pretreated population. The advent of these new therapies have revolutionized the treatment of lung cancer; however, the majority of NSCLC patients still do not respond to PD-1/PD-L1 inhibition leaving an unmet need for a large and growing population.Immunotherapy combinations with chemotherapy, radiation therapy, or novel immunomodulatory agents are currently being examined with the hope of achieving higher response rates and improving overall survival rate. Chemotherapy and radiation therapy has been theorized to increase the release of tumor antigen leading to increased responses with immunotherapy. However, cytotoxic chemotherapy and radiation therapy may also destroy actively proliferating T cells. The correct combination and order of therapy is under investigation. The majority of patients who do respond to immunotherapy have a durable response attributed to the effect of adaptive immune system's memory. Unfortunately, some patients' tumors do progress afterward and investigation of checkpoint blockade resistance is still nascent.This review will summarize the latest efficacy and safety data for early and advanced NSCLC in both the treatment-naïve and pretreated settings. The emerging role of immunotherapy for the treatment of small cell lung cancer and malignant mesothelioma will also be discussed.

• A novel mycobacterial Hsp70-containing fusion protein targeting mesothelin augments antitumor immunity and prolongs survival in murine models of ovarian cancer and mesothelioma. J. Yuan, S. Kashiwagi, P. Reeves, et al. 2014;7:15. PubMed · Publisher · Free full text

  Abstract

  Background: Although dendritic cell (DC) vaccines are considered to be promising treatments for advanced cancer, their production and administration is costly and labor-intensive. We developed a novel immunotherapeutic agent that links a single-chain antibody variable fragment (scFv) targeting mesothelin (MSLN), which is overexpressed on ovarian cancer and mesothelioma cells, to Mycobacterium tuberculosis (MTB) heat shock protein 70 (Hsp70), which is a potent immune activator that stimulates monocytes and DCs, enhances DC aggregation and maturation and improves cross-priming of T cells mediated by DCs.

  Methods: Binding of this fusion protein with MSLN on the surface of tumor cells was measured by flow cytometry and fluorescence microscopy. The therapeutic efficacy of this fusion protein was evaluated in syngeneic and orthotopic mouse models of papillary ovarian cancer and malignant mesothelioma. Mice received 4 intraperitoneal (i.p.) treatments with experimental or control proteins post i.p. injection of tumor cells. Ascites-free and overall survival time was measured. For the investigation of anti-tumor T-cell responses, a time-matched study was performed. Splenocytes were stimulated with peptides, and IFNγ- or Granzyme B- generating CD3+CD8+ T cells were detected by flow cytometry. To examine the role of CD8+ T cells in the antitumor effect, we performed in vivo CD8+ cell depletion. We further determined if the fusion protein increases DC maturation and improves antigen presentation as well as cross-presentation by DCs.

  Results: We demonstrated in vitro that the scFvMTBHsp70 fusion protein bound to the tumor cells used in this study through the interaction of scFv with MSLN on the surface of these cells, and induced maturation of bone marrow-derived DCs. Use of this bifunctional fusion protein in both mouse models significantly enhanced survival and slowed tumor growth while augmenting tumor-specific CD8+ T-cell dependent immune responses. We also demonstrated in vitro and in vivo that the fusion protein enhanced antigen presentation and cross-presentation by targeting tumor antigens towards DCs.

  Conclusions: This new cancer immunotherapy has the potential to be cost-effective and broadly applicable to tumors that overexpress mesothelin.

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