Introduction:

Objectives: The primary aim of this work is to study the immunological effectors induced in CIGB-247-vaccinated patients. These effectors include humoral and cellular components of the immune system. Also, the goal of the present investigation is to detect different immunoglobulin classes and subclasses and its specificity for VEGF relevant epitopes, and demonstrate the induction of VEGF-specific and cytotoxic CD8 T lymphocytes. This research has, as an additional objective, the presentation of the first preliminary pieces of evidence of the feasibility to combine CIGB-247 with other anti-cancer treatments.

Methods:

To investigate the vaccine-induced immunological effectors, ELISA and ELISPOT tests were used for monitoring the immune response elicited in cancer patients from the CENTAURO and CENTAURO-2 clinical trials and also those from the compassionate use program.

Results:

Immunization with CIGB-247 elicited VEGF-specific IgM and IgA antibodies. Antibody response maturation was detected in some patients with long term overall survival, indicated by the subclass switching from IgG1 to IgG4. This antibody response blocked the interaction of VEGF with its receptors VEGFR2 and VEGFR1. This specific polyclonal antibody response inhibited the binding between VEGF and the monoclonal antibody bevacizumab, for that reason, it was directed to a relevant epitope on VEGF, implicated in the VEGF-induced proangiogenic activity. The vaccination contributed to normalizing platelet VEGF levels, and produced cytotoxic CD8 T lymphocytes. Some experimental evidence indicated the potential use of CIGB-247 in combination with chemotherapy. Conclusions: All these results allowed for the application of CIGB-247 in phase II clinical trials in combination with other cancer therapeutic treatments.

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