The immune response of 42 gastrointestinal and ovarian cancer patients at 1 month after exposure to murine monoclonal antibodies (B72.3 and CC49) reactive with the tumor-associated antigen TAG-72 was studied. The incidence of human anti-mouse antibody response was 89% to B72.3 and 70% to CC49. To evaluate the antiidiotypic immune response, we developed a serological assay based on affinity chromatography to remove the interference due to the presence of TAG-72, antiisotypic, and antiallotypic immunoglobulins in the serum. Seventy-eight percent of patients who received B72.3 developed an antiidiotypic response; in 33% of the patients, this was the only immune response detected. The antiidiotypic immune response after treatment with CC49 was present in 54% of the patients. Twelve percent of the patients who received CC49 developed an antiidiotypic response in the absence of antiisotypic or antiallotypic immune response. The lower immunogenicity of the variable region of CC49 is encouraging when considering the use of chimeric or humanized antibodies derived from the murine monoclonal antibody CC49 in clinical studies.
BUF/Mna rats develop spontaneous thymomas with nearly 100% incidence in both sexes. While the thymomas in males develop from around 9 months of age, those in females start from 13-15 months of age. To clarify the mechanism of the delay of thymomagenesis in females, the effect of sex hormones on the development of thymomas was examined after either gonadectomy or oestrogen treatment. Prepubertal ovariectomy accelerated the thymoma development in females, whereas orchiectomy did not affect it. An intraperitoneal injection of oestriol (20 mg) into males at 2 months of age remarkably diminished the thymic weight to about one-tenth of age-matched controls at 16 months of age. These results suggest that oestrogen can actually retard the onset of thymoma in spite of genetic control of its incidence. However, oestrogen did not cause thymic involution when it was injected into rats over 9 months of age. Immunohistochemically, there seemed to be no distinct difference in distribution of oestrogen-receptor-bearing epithelial cells between thymomas and 2- to 3-month-old thymuses. The oestrogen sensitivity of the thymus might be destined to be lost, as the thymic epithelial cells start neoplastic changes with the impairment of oestrogen-receptor function.
Summary Various doses (1 ug to 10mg) of oestriol (E3) were intraperitoneally injected into mice immediately after subcutaneous inoculation of an oestrogen receptor-negative lymphoma cell line
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