Harnessing the Iatrogenic Autoimmune Forces by an Off-Label Low-Dose Combined Anti-CTLA-4 Plus Anti-PD-1 Antibody Blockade
A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Immunology".
Deadline for manuscript submissions: 30 July 2024 | Viewed by 461
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
Special Issue Information
Dear Colleagues,
Immune checkpoint inhibitor (ICI) drugs have enabled major improvements in terms of cancer patients’ survival rates and quality of life. Not unexpectedly, ICIs moved from metastatic settings to being used as early as in the neoadjuvant setting in numerous cancer types. Unfortunately, the manipulation of co-inhibitory receptors has also resulted in a safety issue: widespread iatrogenic immunerelated adverse events (irAEs). Autoimmunity is becoming the nemesis of ICI therapies. As neither anti-CTLA-4 nor anti-PD-1 antibodies are tumor-specific, it was proposed that the development of irAEs depends upon the derangement of self-tolerance. In fact, irAEs are very similar to that of a chronic graft‐versus‐host‐disease (GVHD) reaction following allogeneic bone marrow transplantation. This idea paved the way for the adminstration of lower doses of ICI drugs. Harnessing autoimmune forces by an off-label, low-dose combined anti-CTLA-4 plus anti-PD-1 antibody blockade proved to be safer than that of the established protocols without compromising efficacy in 131 unselected stage IV cancer patients who exhausted all conventional treatments. Importantly, low-dose protocols are not only safer than standard ICI treatments but would be affordable to patients or countries who cannot pay the high cost of registered drugs. Notwithstanding, the mechanism of action of irAEs is an understudied area. In this Special Issue, we welcome original research or review articles on novel molecular biology methods and new techniques to verify the pathogenic mechanism as to why the use of ICIs induces an uncontrolled T cell activation that breaks up tolerance to healthy self‐tissues. Furthermore, we welcome articles as how to break therapy resistance of patients who respond poorly to ICI therapy.
Prof. Dr. Tibor Bakacs
Guest Editor
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Keywords
- immune checkpoint inhibitor (ICI) drugs
- tolerance breakdown
- uncontrolled T cell activation
- immune-related adverse events (irAEs)
- harnessing autoimmune forces
- low-dose anti-CTLA-4 and anti-PD-1 antibodies
- mechanism of action of irAEs
