Inhibition of leukocyte migration by human breast‐cancer‐associated antigens

Abstract

The existence of CMI to tumor-associated antigens present in 3 M KCl extracts of breast carcinomas was demonstrated in a group of breast cancer patients by the leukocyte migration inhibition (LMI) assay. When crude KCl extracts were tested, 3 of 5 breast cancer patients gave a positive response to autologous tumor extracts. Eleven of 20 gave a positive response to allogeneic extracts as compared to 3 of 22 controls (including 6 patients with benign breast disease, 7 with non-mammary cancers and 9 normal controls). Extracts of fibrocystic disease tissue gave positive LMI tests in 2 of 5 breast cancer patients, suggesting the presence of antigenic cross-reactivity between benign and malignant breast disease. An extract of a medullary carcinoma of breast was fractionated on Sephadex G-200 and the effluent pooled into three fractions. The high molecular weight fraction produced LMI in 11 of 22 breast cancer patients and in 1 of 19 controls, including patients with benign breast disease, other cancers and normal individuals. The low molecular weight fraction produced LMI in both the benign (4 of 6) and the malignant breast disease (6 of 20) patients, but not in the controls (0 of 12). A simple fractionation technique has thus separated "cancer-specific" from "organ-specific" activity. Sephadex G-200 fractions were active at a much lower protein concentration than the crude 3 M KCl extracts.

Organ-related and malignancy-associated reactivity of cancer patients' leucocytes: a leucocyte migration study with tumour and foetal extracts

“…The actual nature of the antigens eliciting the LMT reaction is virtually unknown, since most of the pertinent studies rely on the use of unfractionated extracts derived from human tumour tissue or tumour cell lines. It was only in breast cancer that biochemically defined substances were confronted with tumour-bearers' leucocytes (Black et al, 1976;Kadish et al, 1976;McCoy et al, 1978). However, even in this condition no unequivocal identification of the relevant antigen was achieved.…”

Antibodies Conjugated to Potent Cytotoxins as Specific Antitumor Agents

“…The first is the category of antigens that are tissue-specific, provided of course that the tissue from which the tumor originates is non-vital. Breastspecific antigens found on normal and neoplastic mammary epithelial cells exemplify this type of potential target (Thompson et al 1976, Kadish et al 1976, Peterson et al 1978. The second is the category of clonal antigens -antigens that distinguish the progeny of one progenitor cell in a tissue from the progeny of another.…”

“…Breastspecific antigens found on normal and neoplastic mammary epithelial cells exemplify this type of potential target (Thompson et al 1976, Kadish et al 1976, Peterson et al 1978. In particular, two categories of antigen might contain suitable targets for in vivo therapy in the absence of tumor-specific antigens.…”

Leukocyte migration inhibition test in breast cancer patients treated with conventional therapy or with conventional therapy plus poly A � poly U

“…LMIT with tumor extract has frequently been used for the study of cellular immunity in breast cancer patients (Andersen et al, 1969;Wolberg, 1971;Cochran et al, 1973;McCoy et al, 1974McCoy et al, , 1976Jones and Turnbull, 1975;Brandes and Goldenberg, 1976;Kadish et al, 1976;Rieche et al, 1976;Dean et al, 1977). Most of these studies were performed with homologous extracts and they did not provide convincing data in favor of the prognostic value of the test, because of a small number of patients or a short follow-up period.…”