Response to "An innovative mesothelioma treatment based on mir-16 mimic loaded EGFR targeted minicells (TargomiRs)"

Our plain-English summary of Response to "An innovative mesothelioma treatment based on mir-16 mimic loaded EGFR targeted minicells (TargomiRs)", by N. van Zandwijk, J. McDiarmid, H. Brahmbhatt, et al (Translational Lung Cancer Research, 2018).

The study

• Authors: N. van Zandwijk, J. McDiarmid, H. Brahmbhatt, G. Reid
• Journal: Translational Lung Cancer Research
• Published: 2018;7(Suppl 1):S60-S61
• Cited by: 10 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Summary of the article

In this letter, the authors replied to comments by Drs. Viteri and Rosell on their first-in-man, phase 1, open-label, dose-escalation study of microRNA-loaded minicells (TargomiRs) in patients with recurrent malignant pleural mesothelioma, published in Lancet Oncology in October 2017. The commentators had raised two questions: the precise mechanism of action of the treatment, and how it fits among current treatments for mesothelioma. The authors said that a major difficulty was the rapid disappearance of TargomiRs from the circulation after infusion. In preclinical studies in mice and dogs, the minicells accumulated in xenograft tumours 2 hours after administration and were cleared from all sites within 24 hours. The microRNA mimics could not be detected in tumours with existing RT-qPCR platforms. Because biopsies were not planned in the trial, the authors could only theorize that disease control and tumour pain resulted from uptake of the minicells by tumours. They agreed that pre- and post-treatment biopsies will be key. They could not exclude immune reactions to the minicells' LPS-containing surface as an explanation for anti-tumour activity. However, they noted that no responses were seen with cytostatic-loaded minicells, and that inactive controls had no activity in preclinical models. They also accepted that the EGFR-targeting antibody might contribute. They concluded that combination therapy seemed a logical next step and called for carefully designed trials with attention to biomarkers.

PubMed has no abstract for this study, and the article doesn't print one. We wrote this summary from the full article with the help of AI. It is not the authors' wording.

In plain English

This is a letter to the editor, not a new study. In it, the authors replied to comments by Drs. Viteri and Rosell on the authors' own earlier first-in-man, phase 1 trial, published in Lancet Oncology in October 2017. That trial gave TargomiRs to patients with recurrent malignant pleural mesothelioma. TargomiRs are minicells (called EDVs) aimed at the epidermal growth factor receptor (EGFR) and loaded with a microRNA mimic. The letter reported no new patient data and did not study asbestos exposure. The authors acknowledged that their trial was hard to interpret for three reasons: TargomiRs disappeared quickly from the blood, delivery to tumours could not be detected with existing RT-qPCR tests, and biopsies were not planned. As a result, they could only theorize about how the treatment worked. They said they could not exclude that immune reactions shortly after infusion explained the anti-tumour activity. They also agreed that gene therapy, immune effects and the targeting antibody panitumumab might together have been at work. The authors concluded that combination therapy seemed a logical next step and that future trials need biopsies before and after treatment.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: letter to the editor (the authors' reply to comments on their earlier phase 1 trial); no new data
• Who was studied: No new population. The letter discusses the authors' earlier first-in-man, phase 1, open-label, dose-escalation trial in patients with recurrent malignant pleural mesothelioma, published in Lancet Oncology in October 2017.
• Exposure: Not an asbestos exposure study. The treatment discussed is TargomiRs: EGFR-targeted EDVs (minicells) loaded with a microRNA mimic (miR-16 per the title), targeted with the antibody panitumumab.
• The authors' conclusion: The authors concluded that, on the basis of their preclinical data, combination therapy seemed a logical next step in TargomiR development, with carefully planned trials and attention to biomarkers.
• Limitations the authors state:
  • Interpreting the phase 1 data was hampered by the rapid disappearance of TargomiRs from the circulation after infusion.
  • Delivery of the microRNA mimics to tumours could not be detected with existing RT-qPCR platforms.
  • Biopsies were not planned in the trial, so the mechanism of action could only be theorized. The authors agreed that biopsies before and after treatment will be key in future.
  • The authors could not exclude that immune reactions occurring shortly after infusion explained the anti-tumour activity seen.
  • The authors agreed that a combination of gene therapy, immunotherapy and targeting therapy (the EGFR antibody panitumumab) might have contributed to the effects.

Topics

Medical terms in this study, explained in our Lexicon: Mesothelioma, EGFR, Pleural Mesothelioma, Biomarker.

Related studies

• Clinical development of TargomiRs, a miRNA mimic-based treatment for patients with recurrent thoracic cancer — G. Reid, S.C. Kao, et al. (2016)
• Safety and activity of microRNA-loaded minicells in patients with recurrent malignant pleural mesothelioma: a first-in-man, phase 1, open-label, dose-escalation study — N. van Zandwijk, N. Pavlakis, et al. (2017)
• A Significant Metabolic and Radiological Response after a Novel Targeted MicroRNA-based Treatment Approach in Malignant Pleural Mesothelioma — S.C. Kao, M. Fulham, et al. (2015)
• Pemetrexed-loaded nanoparticles targeted to malignant pleural mesothelioma cells: an in vitro study — E. Cova, L. Pandolfi, et al. (2019)
• Microspheres targeted with a mesothelin antibody and loaded with doxorubicin reduce tumor volume of human mesotheliomas in xenografts — S.L. Macura, J.L. Steinbacher, et al. (2013)
• Epidermal growth factor receptor (EGFR)-targeted therapies in mesothelioma — P.L. Chia, A.M. Scott, et al. (2019)

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