Plausible therapeutic benefit of CIMAvax-EGF® in patients with post-COVID-19 respiratory disorders

Authors

Keywords:

CIMAvax-EGF, COVID-19, pulmonary fibrosis.

Abstract

SARS-CoV-2 and its consequences constitute a challenge for global public health. The impact on the structure-function relationship at the lung level is an area of active research, where post-COVID-19 pulmonary fibrosis stands out worryingly. CIMAvax-EGF® is a vaccine that induces a powerful anti-EGF immune response and is used in the treatment of oncological diseases such as lung neoplasms. Clinical trials have demonstrated a strong safety profile, despite this being a vulnerable population. Among the key molecular pathways in fibrosis, transforming growth factor beta stands out for its role, based on its critical activity in myofibroblastic transformation and epithelial-mesenchymal transition; at the molecular level, signaling mediated by the epidermal growth factor receptor is a point of confluence between fibrosis and neoplasms of epithelial origin. In this context, the results of the introduction of CIMAvax-EGF® in the treatment of patients with advanced non-small cell lung neoplasia suggest a clinically significant containment effect. In this manuscript, we address, based on experimental and clinical evidence, the assumptions that rationally justify a measurable therapeutic benefit in patients with post-COVID-19 respiratory disorders, with the use of CIMAvax-EGF®.

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References

1. Zhu N, Zhang D, Wang W, Li X, Yang B, Song J, et al. A novel Coronavirus from patients with pneumonia in China, 2019. N Engl J Med. 2020 [acceso: 01/11/2023]; 382(8):727-33. Disponible en: https://pubmed.ncbi.nlm.nih.gov/31978945/

2. Zhou P, Yang X-L, Wang X-G, Hu B, Zhang L, Zhang W, et al. A pneumonia outbreak associated with a new coronavirus of probable bat origin. Nature. 2020 [acceso: 01/11/2023]; 579(7798):270-3. Disponible en: https://pubmed.ncbi.nlm.nih.gov/32015507/

3. Wu X, Liu X, Zhou Y, Yu H, Li R, Zhan Q, et al. 3-month, 6-month, 9-month, and 12-month respiratory outcomes in patients following COVID-19-related hospitalisation: a prospective study. Lancet Respir Med. 2021 [acceso: 01/11/2023];9(7):747-54. Disponible en: https://pubmed.ncbi.nlm.nih.gov/33964245/

4. Myall KJ, Mukherjee B, Castanheira AM, Lam JL, Benedetti G, Mak SM, et al. Persistent post-COVID-19 interstitial lung disease. An observational study of corticosteroid treatment. Ann Am Thorac Soc. 2021 [acceso: 01/11/2023];18(5):799-806. Disponible en: https://pubmed.ncbi.nlm.nih.gov/33433263/

5. Sheng G, Chen P, Wei Y, Yue H, Chu J, Zhao J, et al. Viral infection increases the risk of idiopathic pulmonary fibrosis. Chest. 2020 [acceso: 01/11/2023];157(5):1175-87. Disponible en: https://pubmed.ncbi.nlm.nih.gov/31730835/

6. RPCEC. La Habana: Equipo de Trabajo del Registro Público Cubano de Ensayos Clínicos, Centro Nacional Coordinador de Ensayos Clínicos - MINSAP . CIMAvax-EGF®-convalecientes con trastornos respiratorios post-COVID-19-adultos-Fase II (CORVAXCIM); 2021. [acceso: 01/11/2023]. Disponible en: https://www.rpcec.sld.cu/ensayos/RPCEC00000375-Sp

7. González G, Crombet T, Catalá M, Mirabal V, Hernández JC, González Y, et al. A novel cancer vaccine composed of human-recombinant epidermal growth factor linked to a carrier protein: Report of a pilot clinical trial. Ann Oncol. 1998 [acceso: 01/11/2023]; 9(4):431-5. Disponible en: https://pubmed.ncbi.nlm.nih.gov/9636835/

8. González G, Crombet T, Neninger E, Viada C, Lage A. Therapeutic vaccination with epidermal growth factor (EGF) in advanced lung cancer: Analysis of pooled data from three clinical trials. Hum Vaccin. 2007 [acceso: 01/11/2023]; 3(1):8-13. Disponible en: https://pubmed.ncbi.nlm.nih.gov/17204867/

9. Neninger E, Verdecia BG, Crombet T, Viada C, Pereda S, Leonard I, et al. Combining an EGF-based cancer vaccine with chemotherapy in advanced nonsmall cell lung cancer. J Immunother. 2009 [acceso: 01/11/2023];32(1):92-9. Disponible en: https://pubmed.ncbi.nlm.nih.gov/19307998/

10. Vinageras EN, de la Torre A, Rodríguez MO, Ferrer MC, Bravo I, del Pino MM, et al. Phase II randomized controlled trial of an epidermal growth factor vaccine in advanced non-small-cell lung cancer. J Clin Oncol. 2008 [acceso: 01/11/2023];26(9):1452-8. Disponible en: https://pubmed.ncbi.nlm.nih.gov/18349395/

11. Rodriguez PC, Popa X, Martínez O, Mendoza S, Santiesteban E, Crespo T, et al. A phase III clinical trial of the epidermal growth factor vaccine CIMAvax-EGF as switch maintenance therapy in advanced non-small cell lung cancer patients. Clin Cancer Res. 2016 [acceso: 01/11/2023];22(15):3782-90. Disponible en: https://pubmed.ncbi.nlm.nih.gov/26927662/

12. Evans R, Lee K, Wallace PK, Reid M, Muhitch J, Dozier A, et al. Augmenting antibody response to EGF-depleting immunotherapy: Findings from a phase I trial of CIMAvax-EGF in combination with nivolumab in advanced stage NSCLC. Front Oncol. 2022 [acceso: 09/11/23]; 12:958043. Disponible en: http://dx.doi.org/10.3389/fonc.2022.958043

13. Al-Habeeb F, Aloufi N, Traboulsi H, Liu X, Nair P, Haston C, et al. Human antigen R promotes lung fibroblast differentiation to myofibroblasts and increases extracellular matrix production. J Cell Physiol. 2021 [acceso: 09/11/23]; 236(10):6836-51. Disponible en: https://pubmed.ncbi.nlm.nih.gov/33855709/

14. Wei S-G, Yu Y, Felder RB. TNF-a-induced sympathetic excitation requires EGFR and ERK1/2 signaling in cardiovascular regulatory regions of the forebrain. Am J Physiol Heart Circ Physiol. 2021 [acceso: 09/11/23]; 320(2):H772-86. Disponible en: https://pubmed.ncbi.nlm.nih.gov/33337962/

15. Zhao C, Yang L, Zhou F, Yu Y, Du X, Xiang Y, et al. Feedback activation of EGFR is the main cause for STAT3 inhibition-irresponsiveness in pancreatic cancer cells. Oncogene. 2020 [acceso: 01/11/2023]; 39(20):3997-4013. Disponible en: https://pubmed.ncbi.nlm.nih.gov/32242147/

16. Dosch AR, Dai X, Reyzer ML, Mehra S, Srinivasan S, Willobee BA, et al. Combined Src/EGFR inhibition targets STAT3 signaling and induces stromal remodeling to improve survival in pancreatic cancer. Mol Cancer Res. 2020 [acceso: 01/11/2023]; 18(4):623-31. Disponible en: https://pubmed.ncbi.nlm.nih.gov/31949002/

17. Xie L, Liu Y, Xiao Y, Tian Q, Fan B, Zhao H, et al. Follow-up study on pulmonary function and lung radiographic changes in rehabilitating severe acute respiratory syndrome patients after discharge. Chest. 2005 [acceso: 01/11/2023]; 127(6):2119-24. Disponible en: https://pubmed.ncbi.nlm.nih.gov/15947329/

18. Zhuang S, Liu N. EGFR signaling in renal fibrosis. Kidney Int Suppl (2011). 2014; 4(1):70-4. DOI: 10.1038/kisup.2014.13

Published

2024-04-19

How to Cite

1.
Pérez Hernández HJ. Plausible therapeutic benefit of CIMAvax-EGF® in patients with post-COVID-19 respiratory disorders. Rev Cubana Med Milit [Internet]. 2024 Apr. 19 [cited 2025 Jan. 10];53(2):e024026046. Available from: https://revmedmilitar.sld.cu/index.php/mil/article/view/26046

Issue

Section

Opinion Article