USE OF EPIDERMAL GROWTH FACTOR DEPLETING AGENTS IN THE TREATMENT OF CHRONIC OBSTRUCTIVE PULMONARY DISEASE

Abstract

The present invention is related to the fields of Biotechnology and Medicine. Particularly, it describes the use of epidermal growth factor (EGF) deprivation agents that contribute to lowering and/or depleting serum epidermal growth factor levels, which has implications in the treatment of the chronic obstructive pulmonary disease. These agents can be vaccine compositions comprising as active principle the conjugate between recombinant human EGF and a carrier protein.

Claims

1. Use of an epidermal growth factor (EGF)-depleting immunotherapeutic agent in the treatment of the chronic obstructive pulmonary disease.

2. Use according to claim 1 wherein the immunotherapeutic agent is a vaccine composition that induces the production of specific antibodies against the EGF.

3. Use according to claim 2, wherein the vaccine composition comprises as an active principle the conjugate between the recombinant human EGF and a carrier protein.

4. Use according to claim 3 wherein the carrier protein is selected from the group comprising: cholera toxin B subunit tetanus toxoid, KLH and P64k from Neisseria meningitidis.

5. Use according to claim 3 wherein the vaccine composition additionally has an adjuvant that is selected from the group comprising: incomplete Freund's adjuvant, squalene based adjuvants, adjuvants of synthetic origin, adjuvants of mineral origin, adjuvants of plant origin, adjuvants of animal origin, particulate proteic adjuvants and liposomes.

6. A method for treating a subject in need thereof comprising the administration of the vaccine compositions of any of claims 2-5 by intramuscular route at a dose range between 20-70 μL/kg, with the first four doses being administered every 14 days and the remaining ones every 28 days for a minimum period of 6 months.

Description

BRIEF DESCRIPTION OF THE FIGURES

[0017] FIG. 1. Baseline serum EGF levels in patients with grade III/IV COPD (severe and very severe stages, according to GOLD criteria), compared with untreated and treated with chemotherapy stage III/IV non-small cell lung cancer (NSCLC) patients.

[0018] FIG. 2. Immunodeprivation of serum EGF levels and anti-EGF antibody titers achieved over time in a grade III COPD patient treated with CIMAvax-EGF.

[0019] FIG. 3. Percentage of inhibition of phosphorylation by anti-EGF antibodies.

EXAMPLES

Example 1. Both COPD Patients and NSCLC Patients have High Baseline Serum EGF Levels

[0020] The baseline serum EGF levels of a sample of patients with grade III/IV COPD and a group of NSCLC patients were determined by ELISA (Gonzalez, E C et al. J Immunoassay Immunochem. (2016) 16: 1-12). Similar levels of serum EGF were found in COPD and NSCLC patients (FIG. 1).

Example 2. Treatment with CIMAvax-EGF Induces Anti-EGF Antibodies while Immunodeprivation Serum EGF and Improving the Clinical Symptoms of COPD

[0021] A patient with severe COPD (grade III according to the GOLD criteria) was immunized with 2.4 mg of the active ingredient of the therapeutic vaccine CIMAvax-EGF, receiving a total of five doses intramuscularly. The anti-EGF antibody titers were quantified by ELISA (Gonzalez G. A. et al. Ann Oncol (1998); 9: 431-435). Serum EGF levels during treatment were determined by ELISA (Gonzalez, E C et al. J Immunoassay Immunochem. (2016) 16: 1-12).

[0022] FIG. 2 shows that immunodeprivation of serum EGF levels related to an increase in anti-EGF antibody titers in the patient was achieved during treatment.

[0023] Additionally, spirometry was performed before starting and after finishing the treatment with the vaccine. Table 1 shows the results of FEV1 the best indicator of the severity of airflow obstruction.

TABLE-US-00001 TABLE 1 FEV1 behavior of a patient with grade III COPD treated with CIMAvax-EGF. Treatment with CIMAvax-EGF FEV1% GOLD criteria Before 48 Grade III severe greater than or equal to 30% and less than 50% After 60 Grade II moderate greater than or equal to 50% and less than 80%

[0024] As can be seen in the results displayed in Table 1, treatment with CIMAvax-EGF improved the clinical respiratory symptoms in the treated patient, decreasing the degree of severity according to GOLD criteria.

Example 3. Treatment with CIMAvax-EGF Induces Anti-EGF Antibodies with the Ability to Inhibit EGF Receptor Phosphorylation

[0025] A patient with severe COPD (grade III according to GOLD classification) was immunized with 2.4 mg of the active ingredient of the therapeutic vaccine CIMAvax-EGF, receiving a total of 8 doses intramuscularly. The inhibition capacity of the serum obtained previously to the first immunization and on the fifth immunization was assessed by means of the Western Blot technique, incubating them for one hour with tumor cells expressing the EGF receptor. The AG1478 antibody was used as inhibition control. FIG. 3 shows that the antibodies generated with the vaccination inhibit the EGF receptor phosphorylation in the presence of EGF (36% inhibition).