GRANULOCYTE MACROPHAGE-COLONY-STIMULATING FACTOR AUGMENTS THE INDUCTION OF ANTIBODIES, ESPECIALLY ANTIIDIOTYPIC ANTIBODIES, TO THERAPEUTIC MONOCLONAL-ANTIBODIES

A group of 86 patients with advanced colorectal carcinoma were treated with the mouse (m) (IgG2A) or chimeric (c) monoclonal antibody (mAb) 17-1A. Prior to therapy, no patient had detectable levels of antibodie s to mAb17-1A. All mmAb17-1A-treated patients (n = 76) developed antib odies against both idiotypic and isotypic determinants. Addition of gr anulocyte/macrophage-colony-stimulating factor (GM-CSF) to mmAb17-1A s ignificantly enhanced the induction of anti-idiotypic (ab(2)) as well as anti-isotypic antibodies. Of the mmAb 17-1A-treated patients, 16 de veloped type I allergic reactions. These patients had significantly hi gher concentrations of anti-(mouse Ig) antibodies than patients withou t type I reactions. Of these 16 patients, 5 had received mmAb17-1A alo ne; they constituted 9% of this group (5/56). The remaining 11 patient s had been given mmAb17-1A together with GM-CSF, and represented 55% o f this treatment group (11/20). The difference was statistically signi ficant (P < 0.001). Of 10 patients, 9 (90%) treated with cmAb17-1A and GM-CSF developed ab(2). The ab(2) concentration in this patient group was significantly lower compared to those treated with mmAb-17A. Anti -(mouse Ig) antibodies caused clinical symptoms requiring therapeutic intervention in fewer than 10% of the patients treated with mmAb17-1A alone. With the addition of GM-CSF, the antibody concentration as well as the frequency of allergic side-effects calling for medical action increased significantly. Significantly more patients with a high ab(2) concentration (at least 15 mu g/ml) 1 month after completion of mAb t herapy responded to mAb treatment as compared to those with a low ab(2 ) concentration (P < 0.05). Moreover, patients with a high ab(2) conce ntration (at least 15 mu g/ml) had a median survival time of 15 months while those with a lower concentration survived for a median time of 9 months (P = 0.01).