Autoimmunization to Epidermal Growth Factor, a component of the immunological homunculus

Gonzalez, Gabriela; Montero, Enrique; León, Kalet; Cohen, Irun R.; Lage, Agustín

doi:10.1016/s1568-9972(01)00015-5

Cited by 28 publications

(27 citation statements)

References 26 publications

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“…B, representative immunoblots showing the phosphorylation levels of EGFR in cells incubated with sera from a control and a vaccinated patient at different time points. (17) to evaluate the immunodominance of the antibody response induced by vaccination. Antibodies to all peptides existed in the natural response before vaccinations.…”

Section: Resultsmentioning

confidence: 99%

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

García

Neninger

Torre

et al. 2008

Clinical Cancer Research

108

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Purpose: Epidermal growth factor (EGF) might be a suitable immunotherapeutic target in nonŝ mall-cell lung cancer (NSCLC). Our approach consists of active immunotherapy with EGF. The aim of the study is to characterize the humoral response and its effects on signal transduction in relation with the clinical outcome. Experimental Design: Eighty NSCLC patients treated with first-line chemotherapy were randomized to receive the EGF vaccine or supportive care. EGF concentration in sera, anti-EGF antibodies and their capacity to inhibit the binding between EGF/EGF receptor (EGFR), and the EGFR phosphorylation were measured. Results: Seventy-three percent of vaccinated patients developed a good antibody response, whereas none of the controls did. In good antibody-responder patients, self EGF in sera was significantly reduced. In 58% of vaccinated patients, the post-immune sera inhibited EGF/EGFR binding; in the control group, no inhibition occurred. Post-immune sera inhibited the EGFR phosphorylation whereas sera from control patients did not have this capacity. Good antibodyresponder patients younger than 60 years had a significantly better survival. A high correlation between anti-EGF antibody titers, EGFR phosphorylation inhibition, and EGF/EGFR binding inhibition was found. There was a significantly better survival for vaccinated patients that showed the higher capacity to inhibit EGF/EGFR binding and for those who showed an immunodominance by the central region of EGF molecule. Conclusions: Immunization with the EGF vaccine induced neutralizing anti-EGF antibodies capable of inhibiting EGFR phosphorylation. There was a significant positive correlation between antibody titers, EGF/EGFR binding inhibition, immunodominance of anti-EGF antibodies, and survival in advanced NSCLC patients.

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Section: Resultsmentioning

confidence: 99%

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

García

Neninger

Torre

et al. 2008

Clinical Cancer Research

108

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“…The geometric mean of patient's baseline anti-EGF antibodies was of 1:224. As we have previously published, 16 these natural antibodies are EGF-specific in the sense that they can be blocked in the assay with added EGF. After EGF vaccination, 3% of vaccinated patients at least doubled their baseline anti-EGF antibody titers (considered as seroconversion), and 49% increased their baseline levels up to 4 fold, with titers >1:4000 being considered GAR.…”

Section: Resultsmentioning

confidence: 99%

Therapeutic Vaccination with Epidermal Growth Factor (EGF) in Advanced Lung Cancer: Analysis of Pooled Data from Three Clinical Trials

Gonzalez¹,

Crombet²,

Neninger³

et al. 2007

Human Vaccines

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KEy wordscancer vaccine, epidermal growth factor, non-small cell lung cancer AbbrEViATioNs AbsTrACTWe have undertaken the analysis of pooled data from three pilot clinical trials of vaccination with Epidermal Growth Factor (EGF) in patients with advanced non small cell lung cancer (NSCLC), addressing particularly the issue of the relationship between immunization and survival. Eighty-three patients with advanced disease were included in three pilot clinical trials and vaccinated with the EGF Vaccine. The trials were designed to evaluate the immunogenicity and safety of the vaccine using different adjuvants, cyclophosphamide pretreatment or not, and different dosage levels of the vaccine. The vaccine elicited specific anti-EGF antibody titers in 83% of subjects, and 49% developed a good anti-EGF antibody response. The adjuvant, the vaccine dose, and cyclophosphamide pretreatment significantly influenced immunogenicity. Patients that seroconverted survived significantly longer than patients who did not. Good antibody responders survived significantly longer than poor responders. Pooled results from these trials confirm that vaccination with EGF is safe and immunogenic in advanced NSCLC patients. The association between good antibody responses and survival consistently appeared in every single trial independently of the specific trial designs. Although these were small pilot nonrandomized clinical trials not intended to confirm therapeutic effect, the survival of the pooled patient population was statistically greater compared with 163 control patients receiving standard treatment.

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“…This is not the case with regard to tumor immunotherapy; here it might be helpful to abolish the down-regulation of immunity enjoyed by a tumor and activate a tumor-specific autoimmune rejection [38,39]. We are currently investigating this possible approach to tumor immunotherapy [40]. Fig.…”

Section: Discussionmentioning

confidence: 99%

Regulation of experimental autoimmune encephalomyelitis by CD4+, CD25+ and CD8+ T cells: analysis using depleting antibodies

Montero

Nussbaum

Kaye

et al. 2004

Journal of Autoimmunity

102

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Autoimmunization to Epidermal Growth Factor, a component of the immunological homunculus

Cited by 28 publications

References 26 publications

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

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

Therapeutic Vaccination with Epidermal Growth Factor (EGF) in Advanced Lung Cancer: Analysis of Pooled Data from Three Clinical Trials

Regulation of experimental autoimmune encephalomyelitis by CD4+, CD25+ and CD8+ T cells: analysis using depleting antibodies

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