Richard P. McCabe

Clinical pharmacology and tissue disposition studies of131I-labeled anticolorectal carcinoma human monoclonal antibody LiCO 16.88

AbstractAntibody LiCO 16.88 is a human IgM recognizing a 30- to 45-kDa intracytoplasmic antigen present in human adenocarcinoma cells. An 8-mg sample of antibody labeled with 5 mCi131I was co-administered i. v. with 120 mg (three patients), 240 mg (three patients) or 480 mg (four patients) unlabeled antibody as a 4-h infusion. The plasma half-life was 24±1.2 h and the immediate apparent volume of distribution was 5.2±0.2 l at the 28-mg dose level. The plasma half-lives and the cumulative urinary excretion of radiolabel did not seem to vary significantly with increasing doses of unlabeled antibody. However, both the volume of distribution and the clearance rate from plasma increased significantly with increasing antibody dose. Uptake of antibody into tumor tissues obtained during laparotomy 8–9 days after administration varied between 0.00002% ID/g and 0.00127% ID/g. In five of seven patients, the tumor content of antibody was higher than that in adjacent normal tissue. Tumor-to-normal tissue ratios ranged from 0.8 to 10 (

The mechanism of leukoregulin enhancement of target cell susceptibility to NK cell mediated cytotoxicity in humans.

\bar x

Generation of Tumor Cell-reactive Human Monoclonal Antibodies Using Peripheral Blood Lymphocytes from Actively Immunized Colorectal Carcinoma Patients

=3.8±1.0). In general, the higher radioactivity(cpm)/g tumor was confirmed by both immunoperoxidase and autoradiography. Antibody 16.88 localizes in tumors after administration and may be considered for use in radioimmunotherapy trials.

Leukoregulin, a Direct-acting Anticancer Immunological Hormone That Is Distinct from Lymphotoxin and Interferon

Significant progress has been made in the application of monoclonal antibody technology to clinical diagnosis of cancer and to management of the disease. Antibodies labeled with radioactive isotopes have been demonstrated to localize in tumors of the gastrointestinal tract (1–6), ovary (6), breast (6,7), and skin (8) and promise to be very helpful in identifying metastases in patients with these tumors. However, there remain several problems to be resolved before radiolabeled antibody detection of tumor foci will be applied as an accepted and routine diagnostic/prognostic procedure. Problems include antibody cross-reactivity with normal tissues (5,6,9,10), low level penetration of antibody into tumor tissue (5,9,10), and inhibitory effects of specific circulating antigen (11). Current research is focused on selecting antibodies with the most desirable characteristics for tumor detection, improving chemistries to allow use of more appropriate radionuclides, and defining the effective clinical applications with regard to the tumor types, tumor sites and available diagnostic equipment and procedures.

Preclinical Studies on the Pharmacokinetic Properties of Human Monoclonal Antibodies to Colorectal Cancer and Their Use for Detection of Tumors

Leukoregulin is an anticancer immunologic hormone or lymphokine whose actions include the inhibition of tumor cell growth and lysis of tumor cells either directly or indirectly by stimulating target cell sensitivity to lysis mediated by natural killer (NK) cells (1, 2, 3). Only a few cell types are directly lysed by leukoregulin and lysis requires very large leukoregulin concentrations. Leukoregulin enhancement of target sensitivity to NK cell cytolysis, however, occurs in the presence of small concentrations of leukoregulin for carcinoma, sarcoma, and leukemia tumor cells (4). Therefore, the primary in vivo means of tumor destruction may be through the combined action of leukoregulin and NK cells.

A Diagnostic-Prognostic Test for Bladder Cancer Using a Monoclonal Antibody-based Enzyme-linked Immunoassay for Detection of Urinary Fibrin(ogen) Degradation Products

SummaryNonimmunized 2/N guinea pigs respond to the presence of chemical carcinogen-transformed syngeneic tumorigenic cells with a sustained (delayed-hypersensitivity-type) 4-day intradermal induration consisting of predominantly polymorphonuclear leukocytes on day 1 and mononuclear cells by day 4, which is independent of the presence of tumor-specific antigens on the tumorigenic cells. Chemical carcinogen-induced morphologically transformed but nontumorigenic cells also induce a polymorphonuclear response by day 1, but neither induration nor a mononuclear response is present on day 4, demonstrating the specificity of the 4-day sustained indurative response for tumorigenic cells. Induration and cellular infiltrates are unaltered if tumor cells are treated prior to injection with the cytostatic lymphokine lymphotoxin or with x-irradiation to inhibit cell proliferation. The intradermal polymorphonuclear leukocyte host response on day 1, but not the mononuclear response on day 4, is also induced by mitomycin C-treated cells or a cytokine culture medium from the cells. No response is present on day 1 or day 4 when cell membranes or lyophilized cells are injected. Thus natural delayed-hypersensitivity-type skin reactivity is a mononuclear leukocyte response specifically directed against intact and metabolically active but not necessarily proliferating tumor cells.