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 111In conjugated murine monoclonal antibodies. Between 1 and 22 mg of antibody containing 1-5 mCi 111In was administered. The populations studied included 30 patients with colorectal carcinoma (four different antibodies), 22 with malignant melanoma (four antibodies), and nine with prostate cancer (two antibodies). Forty-one percent of the patients developed HAMA within 14 days. Three patients (5%) developed an IgM response, 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 56% of the prostate cancer patients. There were no correlations among injected dose, various clinical parameters, and HAMA response. There were 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 idiotypic or isotypic specificity. Only 1/6 patients who were HAMA negative after the first infusion developed HAMA following subsequent infusions of the same monoclonal antibody. Our data demonstrate that a significant percent of cancer patients develop HAMA following a single, low-dose injection of a radiolabeled monoclonal antibody for diagnostic purposes. This may have important implications for the future therapeutic use of monoclonal antibodies in such patients.
Dillman
R O
RO
Hoag Cancer Center, Newport Beach, CA 92663.
Shawler
D L
DL
McCallister
T J
TJ
Halpern
S E
SE
D000818:Animals; D000888:Antibodies, Anti-Idiotypic / Q000096:biosynthesis* / Q000276:immunology; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000276:immunology*; D015179:Colorectal Neoplasms / Q000000981:diagnostic imaging / Q000276:immunology*; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D018796:Immunoconjugates; D007130:Immunoglobulin Idiotypes / Q000096:biosynthesis; D007205:Indium Radioisotopes; D007262:Infusions, Intravenous; D008297:Male; D008545:Melanoma / Q000000981:diagnostic imaging / Q000276:immunology*; D051379:Mice; D011471:Prostatic Neoplasms / Q000000981:diagnostic imaging / Q000276:immunology*; D016719:Radioimmunodetection; D013045:Species Specificity
D000888:Antibodies, Anti-Idiotypic; D000911:Antibodies, Monoclonal; D018796:Immunoconjugates; D007130:Immunoglobulin Idiotypes; D007205:Indium Radioisotopes