CD24: an Anti-Inflammatory Agent for Treatment of COVID-19 Patients

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The researchers at the Tel-Aviv Sourasky Medical Center have successfully completely Phase I trials for the use of CD24 protein delivered in exosomes to treat COVID-19.

Scientists at the Tel-Aviv Sourasky Medical Center have devised a bio-therapeutic agent based on exosomes (membrane bound vesicles) carrying CD24 protein. These exosomes act as a delivery vehicle for the CD24 protein. The exosomes containing CD24 have been isolated and purified from T-REx™-293 cells that have been genetically engineered to over-express CD24. In addition, scientists at OncoImmune Inc. have demonstrated the use of CD24Fc (fusion protein of CD24 with Fc) as a treatment against COVID-19 in clinical trials. 

Attribution: James Heilman, MD, CC BY-SA 4.0 https://creativecommons.org/licenses/by-sa/4.0, via Wikimedia Commons

CD24 is a protein marker that has been shown to overexpress in a wide variety of human cancers1 and the hunt is on for specific anti-CD24 antibodies to combat cancers. However, ironically, in case of COVID-19, scientists have tried to administer CD24 protein to prevent inflammation caused by the cytokine storm and thereby suppressing the COVID-19 disease. The rationale behind using CD24 against COVID-19 disease in patients affected with moderate to severe disease is that CD24 has been implicated in negatively regulating the immune response in acetaminophen induced liver injury model2, where in mice lacking CD24 protein died while normal mice with CD24 protein expression survived. In addition, treatment with CD24Fc (CD24 fused with Fc protein) not only reduced expression of IL-6 and other inflammatory cytokines in in Chinese rhesus macaques (ChRMs) with Simian Immune deficiency Virus infection3, but also protects them against viral pneumonia4.  

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This prompted researchers to use CD24 protein to curb inflammation caused by COVID-19 disease. While scientists at OncoImmune Inc. have used CD24Fc (delivered as IV infusion in normal saline) in a randomized, double-blind, placebo-controlled, multi-site, Phase III study5 to evaluate its safety and efficacy against COVID-19, researchers at the Tel-Aviv Sourasky Medical Center have successfully completely Phase I trials6 for the use of CD24 protein delivered in exosomes to treat COVID-19. The EXO-CD24 was administered to 35 patients as aerosolized in normal saline for inhalation. All 30 patients recovered and 29 of them recovered within 3-5 days. These encouraging results warrant further Phase II and phase III trials to further ensure its safety and efficacy and allow it to be approved by regulators for use in COVID-19 patients. 

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References 

  1. Shapira, S., Finkelshtein, E., Kazanov, D. et al. Integrase-derived peptides together with CD24-targeted lentiviral particles inhibit the growth of CD24 expressing cancer cells. Oncogene (2021). https://doi.org/10.1038/s41388-021-01779-5 
  1. Chen GY, Tang J, Zheng P, Liu Y. CD24 and Siglec-10 selectively repress tissue damage-induced immune responses. Science. 2009 Mar 27;323(5922):1722-5. DOI: https://doi.org/ 10.1126/science.1168988. Epub 2009 Mar 5. 
  1. Tian RR, Zhang MX, Zhang LT, Zhang P, Ma JP, Liu M, Devenport M, Zheng P, Zhang XL, Lian XD, Ye M, Zheng HY, Pang W, Zhang GH, Zhang LG, Liu Y, Zheng YT. CD24 and Fc fusion protein protects SIVmac239-infected Chinese rhesus macaque against progression to AIDS. Antiviral Res. 2018 Sep;157:9-17. DOI: https://doi.org/10.1016/j.antiviral.2018.07.004. Epub 2018 Jul 3. 
  1. Tian RR, Zhang MX, Liu M, Fang X, Li D, Zhang L, Zheng P, Zheng YT, Liu Y. CD24Fc protects against viral pneumonia in simian immunodeficiency virus-infected Chinese rhesus monkeys. Cell Mol Immunol. 2020 Aug;17(8):887-888. DOI: https://doi.org/ 10.1038/s41423-020-0452-5. Epub 2020 May 7. 
  1. CD24Fc as a Non-antiviral Immunomodulator in COVID-19 Treatment (SAC-COVID). Available online at https://clinicaltrials.gov/ct2/show/NCT04317040 
  1. Evaluation of the Safety of CD24-Exosomes in Patients With COVID-19 Infection. Available online at https://clinicaltrials.gov/ct2/show/NCT04747574 

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