HUMAN ANTI-MOUSE ANTIBODY-RESPONSE IN CANCER-PATIENTS FOLLOWING SINGLE LOW-DOSE INJECTIONS OF RADIOLABELED MURINE MONOCLONAL-ANTIBODIES

We examined the human anti-mouse antibody (HAMA) response in 61 cancer patients following a single, diagnostic injection of any one of ten I n-111 conjugated murine monoclonal antibodies. Between 1 and 22 mg of antibody containing 1-5 mCi In-111 was administered. The populations s tudied included 30 patients with colorectal carcinoma (four different antibodies), 22 with malignant melanoma (four antibodies), and nine wi th prostate cancer (two antibodies). Forty-one percent of the patients developed HAMA within 14 days. Three patients (5%) developed an IgM r esponse, five patients (8%) developed an IgG response, and 17 patients (28%) developed both IgM and IgG. Only 27% of the patients with colon cancer developed HAMA, compared to 55% of the melanoma patients and 5 6% of the prostate cancer patients. There were no correlations among i njected dose, various clinical parameters, and HAMA response. There we re variations in the HAMA response to different monoclonal antibodies, but population samples were too small to infer significance. Most of the HAMA responses had a significant proportion of idotypic or isotypi c specificity. Only 1/6 patients who were HAMA negative after the firs t infusion developed HAMA following subsequent infusions of the same m onoclonal antibody. Our data demonstrate that a significant percent of cancer patients develop HAMA following a single, low-dose injection o f a radiolabeled monoclonal antibody for diagnostic purposes. This may have important implications for the future therapeutic use of monoclo nal antibodies in such patients.