PHARMACOLOGICAL ADMINISTRATION OF GRANULOCYTE MACROPHAGE-CALONY-STIMULATING FACTOR IS OF SIGNIFICANT IMPORTANCE FOR THE INDUCTION OF A STRONG HUMORAL AND CELLULAR-RESPONSE IN PATIENTS IMMUNIZED WITH RECOMBINANT CARCINOEMBRYONIC ANTIGEN/

Eighteen colorectal carcinoma patients without macroscopic disease aft er surgery were immunized using recombinant (r) human (h) carcinoembry onic antigen (CEA) with (n = 9) or without (n = 9) the addition of sol uble granulocyte/macrophage-colony-stimulating factor (GM-CSF). The do se of rhCEA per immunization was 100 mu g (n = 6), 316 mu g (n = 6) or 1000 mu g (n = 6). rhCEA was given s.c. on day 1 and 80 mu g/day of G M-CSF s.c. on days 1-4. The schedule was repeated six times during a p eriod of 9 months. All patients in the GM-CSF group developed a strong rhCEA-dose-dependent IgG antibody response while only one-third of th e non-GM-CSF patients mounted a weak antibody response. All patients ( 9/9) in the GMCSF group developed a strong rhCEA-specific proliferativ e T cell response as well as type I T cells (interferon gamma secretio n). In 45% of the patients also a weak type II T cell response (interl eukin-4 secretion) was evoked. Both MHC-class-I- and -II restricted rh CEA-specific T cells were noted. A specific cellular response (prolife ration and/or cytokine secretion) against native hCEA could be found i n 8/9 patients in the GM-CSF group, although at a significantly lower level than against rhCEA, In the non-GM-CSF group a weak rhCEA-specifi c T cell response was induced. Three patients had a proliferative resp onse, 4 patients type I T cells and 6 patients type II T cells. No sig ns of autoimmune reactions were noted. Local pharmacological administr ation of GM-CSF seemed to be a prerequisite for the induction of a str ong immunity against baculovirus-produced hCEA protein. However, the c ellular response against native CEA was of a significantly lower magni tude.