Epidermal growth factor-based cancer vaccine for non-small-cell lung cancer therapy.
BACKGROUND
The role that growth factors and their receptors play in human cancer growth and progression makes them interesting targets for novel treatment modalities. Our approach consisted of active immunotherapy with the epidermal growth factor (EGF). Two pilot clinical trials were conducted to examine the safety and immunogenicity of a five-dose immunization protocol and to compare different adjuvants and treatment designs.


METHODS
Forty patients with advanced non-small-cell lung cancer were enrolled in both trials. They were randomized to be treated with aluminum hydroxide or montanide ISA 51 as adjuvants in the EGF vaccine preparation. The use of cyclophosphamide prevaccination treatment was evaluated in the second trial.


RESULTS
Pooled data from both trials showed that the use of montanide as adjuvant increased the percentage of good antibody responders (GAR). Cyclophosphamide prevaccination treatment did not provoke improvements in antibody response. GAR had a significant increase in survival as compared with poor antibody responders. Response duration was also related to a significant improvement in survival rates.


CONCLUSIONS
Vaccination with five doses of EGF vaccine is safe and immunogenic. Montanide ISA 51 increased the percentage of GAR. There is a direct relationship between anti-EGF antibody titers and immune response duration with survival time.
Gonzalez
G
G
Center of Molecular Immunology, Hermanos Ameijeiras Hospital, Havana, Cuba. gisela@ict.cim.sld.cu
Crombet
T
T
Torres
F
F
Catala
M
M
Alfonso
L
L
Osorio
M
M
Neninger
E
E
Garcia
B
B
Mulet
A
A
Perez
R
R
Lage
R
R
D000276:Adjuvants, Immunologic / Q000008:administration & dosage; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000536:Aluminum Hydroxide / Q000008:administration & dosage; D000917:Antibody Formation; D019496:Cancer Vaccines / Q000009:adverse effects / Q000276:immunology / Q000494:pharmacology*; D002289:Carcinoma, Non-Small-Cell Lung / Q000276:immunology* / Q000628:therapy*; D004815:Epidermal Growth Factor / Q000276:immunology* / Q000494:pharmacology*; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000276:immunology* / Q000628:therapy*; D008297:Male; D008353:Mannitol / Q000008:administration & dosage / Q000031:analogs & derivatives*; D008875:Middle Aged; D009829:Oleic Acids / Q000008:administration & dosage; D016019:Survival Analysis; D014611:Vaccination
D000276:Adjuvants, Immunologic; D019496:Cancer Vaccines; D009829:Oleic Acids; C477385:montanide ISA 51; D008353:Mannitol; D000536:Aluminum Hydroxide; D004815:Epidermal Growth Factor