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Tolerating CD47
Jeffrey S Isenberg1, Enrique Montero2
1Department of Diabetes Complications & Metabolism, Arthur Riggs Diabetes & Metabolism Research Institute, City of Hope National Medical Center, Duarte, California, USA.
Abstract:
Cluster of differentiation 47 (CD47) occupies the outer membrane of human cells, where it binds to soluble and cell surface receptors on the same and other cells, sculpting their topography and resulting in a pleiotropic receptor-multiligand interaction network. It is a focus of drug development to temper and accentuate CD47-driven immune cell liaisons, although consideration of on-target CD47 effects remain neglected. And yet, a late clinical trial of a CD47-blocking antibody was discontinued, existent trials were restrained, and development of CD47-targeting agents halted by some pharmaceutical companies. At this point, if CD47 can be exploited for clinical advantage remains to be determined. Herein an airing is made of the seemingly conflicting actions of CD47 that reflect its position as a junction connecting receptors and signalling pathways that impact numerous human cell types. Prospects of CD47 boosting and blocking are considered along with potential therapeutic implications for autoimmune diseases and cancer.
Insights
Cluster of differentiation 47 (CD47) is a cell surface protein with complex roles in cell interactions. Understanding its dual functions is key to developing new therapies for cancer and autoimmune diseases.
Area of Science:
- Immunology
- Cell Biology
- Drug Development
Background:
- Cluster of differentiation 47 (CD47) is a cell surface protein involved in cell-cell interactions.
- CD47 plays a role in immune responses and is a target for drug development.
- Previous clinical trials of CD47-blocking antibodies have faced setbacks.
Purpose of the Study:
- To explore the complex and seemingly conflicting roles of CD47.
- To investigate the therapeutic potential of modulating CD47 activity.
- To consider implications for autoimmune diseases and cancer.
Main Methods:
- Review of existing literature on CD47.
- Analysis of CD47's position as a junction for receptor-ligand interactions.
- Consideration of signaling pathways influenced by CD47.
Main Results:
- CD47 exhibits pleiotropic effects due to its extensive receptor-multiligand network.
- On-target effects of CD47 modulation are often overlooked.
- CD47's dual role as a connector of receptors and signaling pathways impacts various cell types.
Conclusions:
- The clinical utility of CD47 modulation (both blocking and boosting) requires further investigation.
- CD47's complex functions present both challenges and opportunities for therapeutic intervention.
- Targeting CD47 may offer potential benefits for autoimmune diseases and cancer treatment.
