Challenges of Immune Checkpoint Inhibitor Therapy
A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Pathology, Diagnostics, and Therapeutics".
Deadline for manuscript submissions: 30 November 2024 | Viewed by 267
Special Issue Editor
Interests: using low-dose immune checkpoint blockade in combination with oncolytic viruses for the treatment of advanced cancer; using apathogenic viruses for controlling unrelated viral diseases
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Special Issue Information
Dear Colleagues,
The immune system attacks foreign substances (non-self) by inflammation, while it tolerates normal tissues (self). Natural inhibitory feedback loops, i.e., immune checkpoints, reduce inflammation following immune activation. After successful vaccination programs against xenogeneic infectious diseases, the assumption was that host immunity would also be protective against isogeneic cancer. For a century, however, cancer immunotherapy trials have failed. Eventually, immune checkpoint inhibitor (ICI) drugs resulted in an immunotherapy revolution such that 43.6% of US cancer patients are eligible for ICI therapy. Unfortunately, the price to pay for such a spectacular success was the impairment of self-tolerance. Widespread iatrogenic immune-related adverse events (irAEs) are becoming the nemesis of ICI therapies. It was proposed that irAEs are very similar to that of a chronic graft-versus-host-disease (GVHD) reaction following allogeneic bone marrow transplantation. This idea has paved the way for the administration of ultra-low doses of ICI drugs (ipilimumab 0.3 mg/kg plus nivolumab 0.5 mg/kg), which proved to be safer than that of the established protocols (irAEs of WHO Grade 3 and 4: in 6.11% and 2.29% of patients), without compromising efficacy (median overall survival: 19.3 months) in 131 unselected stage IV cancer patients with 23 different histological types of cancer who exhausted all conventional treatments. Ultra-low dose protocols are not only safer than standard ICI treatments, but are affordable to patients or countries who cannot pay the high cost of registered drugs. In this Special Issue, we welcome original research or review articles on molecular biology methods and techniques to verify the pathogenic molecular mechanism of irAEs. We also welcome articles proposing cost saving de-escalation studies to increase the safety of and access to highly effective ICI medications.
Prof. Dr. Tibor Bakacs
Guest Editor
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Keywords
- immune checkpoint inhibitor
- ICI
- safety of ICI drugs
- irAE of ICI drugs
- ultra-low-dose ICI
- cost saving with ICI drugs
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