CLINICAL AND IMMUNOLOGICAL EFFECTS OF MONOCLONAL-ANTIBODY CC49 AND INTERLEUKIN-2 IN PATIENTS WITH METASTATIC COLORECTAL-CANCER

We examined the possibility that prior exposure to the murine monoclon al antibody (mAb), CC49, which recognizes the pancarcinoma antigen, TA G-72, would modify the clinical activity of interleukin-2 (IL-2) in pa tients with metastatic colorectal cancer, Fourteen patients received 2 mg of unconjugated CC49 on Day 1; on Day 22, they began human recombi nant IL-2 at 1 mg/m(2)/day for 4 days by continuous IV infusion, Four- day cycles of IL-2 were repeated weekly for 8 weeks unless there was e vidence of unacceptable toxicity or progressive disease, Therapy was w ell tolerated, Proliferative responses of peripheral blood mononuclear cells (PBMC) to CC49, its Feb fragment, isotype matched marine immuno globulin, and CC49 complexed with TAG-72(+) mucin increased after CC49 administration (Day 21), These proliferative responses decreased afte r IL-2 administration, PBMC proliferative responses to AI49, an anti-C C49 idiotype antibody (Ab(2)), and TAG-72(+) mucin was not induced, No complete or partial clinical responses were observed; one patient man ifested a transient mixed response, A single infusion of CC49 does hav e biologic activity; it is, however, unlikely to substantially modify tumor response rates effected by IL-2 in patients with metastatic colo rectal cancer.