TGFα CANCER VACCINE.

Transforming Growth Factor alpha (TGFα) is an endogenous growth factor that is associated with the loss of growth regulation of the transformed phenotype and its action is by the interaction with the epidermal growth factor (EGF) receptor. Also this molecule is over-expressed by carcinomas as a tumor-associated antigen. In this regard the principal goal of this work is to development an active immunoteraphy capable to block the autocrine loop TGFα-EGFR and/or to elicit a specific cellular response against tumor that over-expressed this growth factor. To our knowledge TGFα has not been used in active specific cancer immunotherapy. A new vaccine containing a fusion protein between human TGFα (hTGFα) and P64k from Neisseria meningitidis, was generated and characterized in a mouse model using different adjuvants. Interestingly a good correlation between anti-hTGFα serum antibody titers, mainly IgG, and antibody secreting B cells in the lymph nodes of immunized mice was seen. The isotype profile of hTGFα-specific antibody responses was similar when Freund adjuvant complete or incomplete was used showing increase levels of IgG2a and IgG2b immunoglobulins respect to aluminum hydroxide. Noteworthy, those anti-hTGFα antibodies recognize the hTGFα precursor in cell line expressing this growth factor. For 4 peptide represent the different loops of hTGFα tested, serum from immunized mice mainly recognize the C-loop and C-terminal region. That region is important in the TGFα/EGF-R binding. Not crossreactivity against human or murine epidermal growth factor (EGF) was found. [ABSTRACT FROM AUTHOR]