Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

Keynote webinar | Spotlight on medication adherence

LIVE: Thursday 27th June 2024, 18:00-19:30 (CEST)
Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.
ADVANCED SEARCH
Log in
Top
World Journal of Surgical Oncology
Published in: World Journal of Surgical Oncology 1/2013

Open Access 01-12-2013 | Research

Effect of blockade of the EGF system on wound healing in patients vaccinated with CIMAvax® EGF

Authors: Aymara Fernández Lorente, Soraida Acosta Brooks, Elia Neninger Vinageras, María del Carmen Barroso Alvarez, Barbara Wilkinson Brito, Mayelin Troche Concepción, Liana B Martínez Pérez, Carmen E Viada González, Tatiana Crespo Diaz, Angel Raymundo Casacó Parada

Published in: World Journal of Surgical Oncology | Issue 1/2013

Login to get access

Abstract

Background

The epidermal growth factor receptor (EGFR) signaling system is frequently unbalanced in human malignancies due to increased ligand production, receptor overexpression, receptor mutations, and/or cross-talk with other receptor systems. For this reason, the EGFR is an attractive target for anticancer therapy. The epidermal growth factor also plays an important role in regulating multiple facets of cutaneous wound healing, including inflammation, wound contraction, proliferation, migration, and angiogenesis. In the Center of Molecular Immunology, a cancer vaccine is produced (CIMAvax® EGF) that blocks the binding of EGF to its receptor. This blockade causes a significant inverse association between the anti-EGF antibody titers and EGF concentration. Around 1,500 patients with non-small cell lung cancer have been treated, showing that this vaccine is safe, immunogenic, increases survival and improves quality of life. Taking into account the therapeutic benefits of CIMAvax® EGF vaccination and the role of EGF-EGFR system in the wound healing process, we decided to conduct a retrospective research with the aim of determining the effect to the CIMAvax® EGF vaccine on the wound healing process in patients undergoing surgical treatment.

Methods

Medical records of 452 vaccinated patients were reviewed and only six patients receiving surgical treatment were identified. Further information about these six patients was obtained from source documents, including medical records and operative reports using an observational list that included different variables. Post-surgical wound healing complications were identified using the National Cancer Institute Common Toxicity Criteria for Adverse Events (NCI-CTC) version 3.0.

Results

None of the six patients operated on presented adverse events related to the wound healing, that is to say, no wound dehiscence, wound infection, delayed wound healing, fistula formation, abscess formation or hemorrhage/bleeding associated with surgery during treatment with CIMAvax® EGF occurred.

Conclusions

These results suggest that the use of CIMAvax® EGF does not produce a deleterious effect in the wound healing process.
Literature
1.
Wong AJ, Ruppert JM, Bigner SH: Structural alterations of the epidermal growth factor receptor gene in human gliomas. Proc Natl Acad Sci USA. 1992, 89: 2965-2969. 10.1073/pnas.89.7.2965.PubMedCentralCrossRefPubMed
2.
Damstrup L, Kuwada SK, Dempsey PJ: Amphiregulin acts as an autocrine growth factor in two human polarizing colon cancer lines that exhibit domain selective EGF receptor mitogenesis. Br J Cancer. 1999, 80: 1012-1019. 10.1038/sj.bjc.6690456.PubMedCentralCrossRefPubMed
3.
Peghini PL, Iwamoto M, Raffeld M: Overexpression of epidermal growth factor and hepatocyte growth factor receptors in a proportion of gastrinomas correlates with aggressive growth and lower curability. Clin Cancer Res. 2002, 8: 2273-2285.PubMed
4.
Arteaga CL: The epidermal growth factor receptor: from mutant oncogene in nonhuman cancers to therapeutic target in human neoplasia. J Clin Oncol. 2001, 19: 32-40.
5.
Mendelsohn J, Baselga J: Epidermal growth factor receptor targeting in cancer. Semin Oncol. 2006, 33: 369-385. 10.1053/j.seminoncol.2006.04.003.CrossRefPubMed
6.
Greenhalgh DG: The role of growth factors in wound healing. J Trauma. 1996, 41: 159-167. 10.1097/00005373-199607000-00029.CrossRefPubMed
7.
Schultz GS, White M, Mitchell R, Brown G, Lynch J, Twardzik DR, Todaro GJ: Epithelial wound healing enhanced by transforming growth factor- and vaccinia- growth factor. Science. 1987, 235: 350-352. 10.1126/science.3492044.CrossRefPubMed
8.
Steed DL: Modifying the wound healing response with exogenous growth factors. Clin Plast Surg. 1998, 25: 397-405.PubMed
9.
Repertinger SK, Campagnaro E, Fuhrman J, El-Abaseri T, Yuspa SH, Hansen LA: EGFR enhances early healing after cutaneous incisional wounding. J Invest Dermatol. 2004, 123: 982-989. 10.1111/j.0022-202X.2004.23478.x.CrossRefPubMed
10.
Neninger E, de la Torre A, Osorio M, Catalá M, Bravo I, Mendoza M, Abreu D, Acosta S, Rives R, Carrillo C, Gonzalez M, Viada C, García B, Crombet T, Gonzalez G, Lage A: Phase II randomized controlled trial of an epidermal growth factor vaccine in advanced non-small-cell lung cancer. J Clin Onc. 2008, 26 (9): 1452-1458. 10.1200/JCO.2007.11.5980.CrossRef
11.
Gonzalez G, Crombet T, Torres F, Catalá M, Alfonso L, Osorio M, Neninger E, Garcia B, Mulet A, Perez R, Lage A: Epidermal growth factor-based cancer vaccine for non-small-cell lung cancer therapy. Ann Oncol. 2003, 14 (3): 461-466. 10.1093/annonc/mdg102.CrossRefPubMed
12.
Crombet T, Neninger E, Catalá M, García B, Leonard I, Gonzalez G, Pérez R, Lage A: Treatment of NSCLC patients with an EGF-based cancer vaccine: report of a phase I trial. Cancer Biol Ther. 2006, 5 (2): 145-149. 10.4161/cbt.5.2.2334.CrossRef
13.
García B, Neninger E, de la Torre A, Leonard I, Martínez R, Viada C, González G, Mazorra Z, Lage A, Crombet T: Effective inhibition of the epidermal growth factor/epidermal growth factor receptor binding by anti-epidermal growth factor antibodies is related to better survival in advanced non-small-cell lung cancer patients treated with the epidermal growth factor cancer vaccine. Clin Cancer Res. 2008, 14 (3): 840-846. 10.1158/1078-0432.CCR-07-1050.CrossRefPubMed
14.
González G, Lage A, Crombet T, Rodríguez G, García B, Cuevas A, Viña L, Arteaga N, Neninger E: CIMAvax®-EGF: a novel therapeutic vaccine for advanced lung cancer. Biotecnol Apl. 2009, 26 (4):
15.
Gonzalez G, Crombet T, Lage A: Chronic vaccination with a therapeutic EGF-based cancer vaccine: a review of patients receiving long lasting treatment. Curr Cancer Drug Targets. 2011, 11 (1): 103-110. 10.2174/156800911793743583.CrossRefPubMed
16.
Guillen G, Silva R, Alvarez A, Coizeau E, Novoa L, Selman M, Morales J, Musacchio A, del Valle J, Delgado M, Tamayo B, Caballero E, Fernandez JR, Herrera L: Cloning and expression of a high molecular weight protein (PM-6) from the Neisseria meningitidis strain B: 4PL15. Evaluation of the immunogenicity and bacterial activity of antibodies raised against the recombinant protein. Pathology and Immunobiology of Neisseriaceae. Edited by: Conde-Gonzalez CJ, Morse S, Rice P. 1994, Cuernavaca, Mexico: National Institute of Public Health, 834-840.
17.
Silva R, Selman R, Guillén G, Herrera L, Fernandez JR, Novoa L, Morales J, Moreira V, González S, Tamargo B, del Valle JA, Caballero E, Alvarez A, Coizeau E, Cruz S, Musacchio A: Nucleotide sequence coding for an outer membrane protein from Neisseria meningitidis and use of said sequence in vaccine preparations. USA patent. 1994, 5: 286-484.
18.
Rodríguez G, Albisa A, Viña L, Cuevas A, García B, García AT, Portillo A, Calvo L, Crombet T, González G, Chico E: Manufacturing process development for an epidermal growth factor-based cancer vaccine. Int Biopharm. 2008, 21: 2-8.
19.
20.
González G, Crombet T, Catalá M, Mirabal V, Hernández JC, González Y, Marinello P, Guillén G, Lage A: A novel vaccine composed of human-recombinant epidermal growth factor linked to a carrier protein: report of a pilot clinical trial. Ann Oncol. 1998, 9: 431-435. 10.1023/A:1008261031034.CrossRefPubMed
21.
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. Human Vacc. 2007, 3: 8-13. 10.4161/hv.3.1.3537.CrossRef
22.
Neninger E, García B, Crombet T, Viada C, Pereda S, Leonard I, Mazorra Z, Fleites G, González M, Wilkinson B, González G, Lage A: Combining an EGF-based cancer vaccine with chemotherapy in advanced non-small cell lung cancer. J Immunol. 2009, 32: 92-99.
23.
Gabriel A, Mussman J, Rosenberg LZ, de la Torre JI: Wound healing, growth factors. 2009, University School of Medicine, 1-11.
24.
Thomas C: Checklist for factors affecting wound healing. Adv Skin Wound Care. 2011, 24 (4): 192-10.1097/01.ASW.0000396300.04173.ec.CrossRef
25.
Cortes J, Caralt M, Delaloge S, Cortes-Funes H, Pierga JY: Safety of bevacizumab in metastatic breast cancer patients undergoing surgery. Eur J Cancer. 2012, 48 (4): 475-481. 10.1016/j.ejca.2011.11.021.CrossRefPubMed
26.
Barrientos S, Stojadinovic O, Golinko MS, Brem H, Tomic-Canic M: Growth factors and cytokines in wound healing. Wound Repair Regen. 2008, 16: 585-601. 10.1111/j.1524-475X.2008.00410.x.CrossRefPubMed
27.
Rodriguez G, Gonzalez G, Crombet T, Lage A: Therapeutic vaccination with an EGF-based vaccine in lung cancer: a step in the transition to a chronic disease. Expert Rev Respir Med. 2011, 5: 337-342. 10.1586/ers.11.12.CrossRefPubMed
28.
Casacó A, Díaz Y, Ledón N, Merino N, Valdés O, Garcia G, Garcia B, González G, Pérez R: Effect of an egf-cancer vaccine on wound healing and inflammation models. J Surg Res. 2004, 122: 130-134. 10.1016/j.jss.2004.06.008.CrossRefPubMed
29.
Mellor J, Cassumbhoy M, Jefford M: Clinical guidance on the perioperative use of targeted agents in solid tumor oncology. J Clin Oncol. 2011, 7: 106-113.
30.
Casacó A, Fuente D, Ledón N, Fernández A, Crombet T: Anti-epidermal growth factor/epidermal growth factor receptor therapeutic anti-cancer drugs and the wound healing process. J Cancer Sci Ther. 2012, 4: 324-329.CrossRef
31.
Zieske JD, Takahashi H, Hutcheon AE, Dalbone AC: Activation of epidermal growth factor receptor during corneal epithelial migration. Invest Ophthalmol Vis Sci. 2000, 41: 1346-PubMed
32.
Bennett N, Schultz G: Growth factors and wound healing: biochemical properties of growth factors and their receptors. Am J Surg. 1993, 165: 728-10.1016/S0002-9610(05)80797-4.CrossRefPubMed
33.
Metadata
Title
Effect of blockade of the EGF system on wound healing in patients vaccinated with CIMAvax® EGF
Authors
Aymara Fernández Lorente
Soraida Acosta Brooks
Elia Neninger Vinageras
María del Carmen Barroso Alvarez
Barbara Wilkinson Brito
Mayelin Troche Concepción
Liana B Martínez Pérez
Carmen E Viada González
Tatiana Crespo Diaz
Angel Raymundo Casacó Parada
Publication date
01-12-2013
Publisher
BioMed Central
Published in
World Journal of Surgical Oncology / Issue 1/2013
Electronic ISSN: 1477-7819
DOI
https://doi.org/10.1186/1477-7819-11-275

Other articles of this Issue 1/2013

World Journal of Surgical Oncology 1/2013 Go to the issue

Research

Functional tongue reconstruction with the anterolateral thigh flap

Research

Definition of compartment-based radical surgery in uterine cancer: radical hysterectomy in cervical cancer as ‘total mesometrial resection (TMMR)’ by M Höckel translated to robotic surgery (rTMMR)

Research

D2 lymphadenectomy is not only safe but necessary in the era of neoadjuvant chemotherapy

Case report

Primary choriocarcinoma of the colon: a case report and review of the literature

Research

Histopathological and clinical characteristics of duodenal gastrointestinal stromal tumors as predictors of malignancy

Research

Safety of intracorporeal circular stapling esophagojejunostomy using trans-orally inserted anvil (OrVil™) following laparoscopic total or proximal gastrectomy - comparison with extracorporeal anastomosis