PHASE-I CLINICAL-EVALUATION OF A NEW MURINE MONOCLONAL-ANTIBODY (MU-9) AGAINST COLON-SPECIFIC ANTIGEN-P FOR TARGETING GASTROINTESTINAL CARCINOMAS

Background. Colon-specific antigen-p is a tumor-associated antigen pre sent in approximately 60% of colorectal cancers. Preclinical studies h ave shown that the murine monoclonal antibody Mu-9 has excellent tumor -targeting abilities; therefore, clinical studies were initiated. Meth ods. The immunoglobulin G and F(ab')(2) were radiolabeled with I-131, and administered to 13 and 12 patients, respectively, with advanced ga strointestinal cancer (colon, rectal, and pancreatic) for radioimmunod etection or radioimmunotherapy. Results. Even in patients with highly elevated carcinoembryonic antigen levels, only one patient showed appr eciable complexation of the labeled antibody, suggesting the epitope m ay not be highly expressed in the blood. Fifty percent of I-131-Mu-9 i mmunoglobulin G was cleared from the blood within 41 +/- 13 hours, whi le it took only 19 +/- 8 hours for the same amount of I-131-F(ab'(2)) to be cleared from the blood. Lesion detection in the abdomen, liver, and pelvis was greater than 90% for either the immunoglobulin G or F(a b')(2). The dose absorbed by the normal organs, except the kidneys, wa s two- to threefold less for the F(ab')(2) than for the whole immunogl obulin G. The dose to the kidneys was similar for both forms of immuno globulin. The average tumor dose for I-131-Mu-9 immunoglobulin G was 1 3.9 +/- 11.0 cGy/mCi, and for I-131-F(ab')(2) was 4.9 +/- 2.9. Tumor/r ed marrow dose ratios for the whole immunoglobulin G were 4.3 +/- 3.0, compared to 3.3 +/- 1.9 for the F(ab')(2), suggesting the therapeutic window for the two forms of immunoglobulin may be similar. Eight of n ine patients given the whole immunoglobulin G developed highly elevate d levels of human anti-mouse antibody, whereas lower values were obser ved in five of seven patients given the F(ab')(2). Conclusions. These initial results support the need for further evaluation of Mu-9 immuno globulin G and F(ab')(2) for targeting gastrointestinal cancer for rad ioimmunotherapy.