Thirty patients with advanced measurable pancreatic
adenocarcinoma were entered onto a phase II trial with recombinant
interferon gamma (Biogen, Cambridge, MA; 10(6) U/m2 daily for 4 days) and
monoclonal antibody (
Mab) 17-1A (Centocor, Malvern, PA; 150 mg in autologous leukocytes on days 2, 3, and 4 following
interferon infusion). The effect of a single
interferon gamma treatment on natural and antibody-dependent cellular cytotoxicity (ADCC),
Fc receptor occupancy by antibody, and
human leukocyte antigen-DR (
HLA-DR) expression on monocytes and lymphocytes was also studied. Toxicity was modest and generally limited to grade I to II
fever,
nausea and
vomiting, and hepatotoxicity. Five patients were considered to be nonassessable for response. Of the 25 assessable patients, one objective response (complete remission for a duration of 4 months) was observed. Stable disease for 2 months or greater was noted in nine patients. The median survival for the group was 5 months. Analysis of cytotoxicity data obtained prior to treatment showed reduced natural cytotoxic activity in these patients compared with normal volunteers. A significant improvement in natural cytotoxic activity to normal levels occurred within 24 hours following the
interferon gamma infusion. This was also associated with augmented antibody-dependent cellular cytotoxicity. Although
HLA-DR expression was not increased on either monocytes or lymphocytes, an increased capacity of both lymphocytes and monocytes to bind
Mab 17-1A was observed. In all in vitro assays of ADCC, the presence of antibody excess was associated with improved cytolytic activity. In spite of the favorable modulation of cytolytic activity and improved ability of effector cells to bind Mab, we failed to demonstrated adequate clinical efficacy in the treatment of patients with pancreatic
adenocarcinoma using this dose and schedule of
interferon gamma and
Mab 17-1A. Future trials will focus on alternate schedules of
Mab 17-1A with the hope of improving
tumor antigen saturation and circulating levels of infused antibody.