Anti-tumour immunity in malignant melanoma assay by tube leucocyte adherence inhibition

Abstract

Summary.-Tumour antigen-induced inhibition of leucocyte adherence was modified for use in glass test tubes (Tube LAI assay) for the study of cell-mediated antitumour immunity to human malignant melanoma. Peripheral blood leucocytes (PBL) of 20 out of 25 patients (80%) with active malignant melanoma responded to an extract of malignant melanoma with LAI, whereas only 4.5%o of 475 control subjects showed a response. The malignant melanoma patients reacted to both allogeneic and autologous extracts of malignant melanoma which indicates a common cross-reacting antigen. Malignant melanoma patients did not respond to unrelated tumour extracts. The LAI was mediated by PBL (monocytes) " armed" with cytophilic anti-tumour antibody specific for the sensitizing tumour antigen.The anti-tumour response of the malignant melanoma patients was dependent on the stage of the cancer, and 11 out of 13 Stage I patients had a positive NAI, whereas patients with disseminated cancer had decreased response. The diminished LAI in patients with large tumour burdens appeared to be the result of release of tumour antigen systemically. Also, surgery and chemotherapy depressed LAI. Although LAI was depressed after surgical excision of the cutaneous melanoma, most patients showed LAI 1-3 months later. Tumour-free melanoma patients monitored for one year by the Tube LAI assay showed a decline in their anti-tumour immunity 5-6 months after surgery. The NAI was low or negative after the 8th post-surgical month in tumour-free patients. Patients with residual malignant melanoma showed persistent or recurrent LAI after the 8th post-surgical month. LAI reactivity monitored after " curative " surgery for malignant melanoma may assist in determining whether the patient is tumour-free or has a recurrence.

Expression by human fetal organs of organ-specific cancer neoantigens as measured by leukocyte adherence inhibition

“…Once expression of fetal OSN stopped at about 21 weeks, LAI reactivity persisted for about 2 months and then became undetectable. This finding is identical to our previous observation that LAI reactivity of cancer patients disappears 2 to 3 months after successful excision of a cancer [38,56]. In experimental rat tumors, specific LAI reactivity also declines 10 days after thorough excision of the tumors [33].…”

Isolation of breast cancer tumour antigen from serum and urine

“…The sera of patients with early cancer contain tumour-specific cytophilic IgG antibody Marti and Thomson, 1976). Although the concentration in serum of the cytophilic tumour-specific antibody is unknown, it presumably may be quite low since Imir et al (1976) have shown that one ng of specific antibody is sufficient to " arm " mononuclear cells to mediate antibody-dependent cytotoxicity.…”

Leukocyte Adherence Inhibition Assay in the Diagnosis and Follow-Up of Colorectal Cancer Patients

“…Longitudinal analysis of LAI reactivity after surgery was previously reported by Thomson et al [17] and Marti and Thomson [14], They found three main patterns of LAI reactivity, namely: (a) disappearance of LAI activity after surgery, in dicating eradication of disease, (b) negative LAI sec ondary to increase in tumor burden; and (c) emer gence of LAI activity preceding regrowth of cancer. Our results fall in general in the same pattern.…”

“…Since its first description, the assay was adapted to tubes [7,11] and further modified and automated [2,17]. The assay in its various modifications was used to disclose the presence of malignancy [5,6,9,[14][15][16][17] and was found to be inversely related to tumor bur den. Although many reports substantiate the validity of the LAI assay to detect antitumor immune response to human tumor-associated antigens, the diagnostic value of the assay has been questioned [1.…”