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Epidermal growth factor-based cancer vaccine for non-small-cell lung cancer therapy
G Gonzalez1, T Crombet, F Torres
1Center of Molecular Immunology, Hermanos Ameijeiras Hospital, Havana, Cuba. gisela@ict.cim.sld.cu
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.
Patients And 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.
Insights
Active immunotherapy using epidermal growth factor (EGF) vaccine is safe and immunogenic in non-small-cell lung cancer patients. Montanide ISA 51 adjuvant improved antibody response, correlating with increased survival.
Area of Science:
- Oncology
- Immunotherapy
- Cancer Research
Background:
- Growth factors and receptors are key drivers of cancer progression, presenting therapeutic targets.
- Active immunotherapy with epidermal growth factor (EGF) was investigated as a novel treatment modality.
- Two pilot trials assessed the safety and immunogenicity of a five-dose EGF vaccine protocol.
Purpose of the Study:
- To evaluate the safety and immunogenicity of an EGF vaccine in cancer patients.
- To compare the efficacy of different adjuvants (aluminum hydroxide vs. montanide ISA 51).
- To assess the impact of cyclophosphamide prevaccination on immune response.
Main Methods:
- Forty patients with advanced non-small-cell lung cancer participated in the trials.
- Participants were randomized to receive either aluminum hydroxide or montanide ISA 51 as vaccine adjuvants.
- The second trial evaluated cyclophosphamide prevaccination prior to EGF vaccination.
Main Results:
- Montanide ISA 51 significantly increased the proportion of good antibody responders (GAR).
- Cyclophosphamide prevaccination did not enhance antibody response.
- Good antibody responders (GAR) demonstrated significantly improved survival compared to poor responders.
- Response duration was directly correlated with improved survival rates.
Conclusions:
- EGF vaccination (five doses) is safe and elicits an immune response.
- Montanide ISA 51 is a superior adjuvant for enhancing anti-EGF antibody production.
- Higher anti-EGF antibody titers and longer response duration are linked to improved patient survival.