We plan to extend studies with our so far (greater than 350 patients) sensitive and specific immunoassays in the detection (including early) of breast-, lung-, and pancreas adeno carcinoma (CA), and other CAs. We use the human T -- anti-T system to measure cell-mediated (CMI) as well as humoral immune responses towards CA-associated T antigen. T antigen does not occur in reactive form in non-CA tissue. However, it is readily prepared by a multistep procedure and slight chemical degradation from healthy, outdated human red blood cells. Delayed-type skin hypersensitivity to erythrocyte-derived T antigen as well as humoral anti-T response to T, measured by a novel quantitative immunofluorescent assay using insolubilized T antigen (SPIA-T), had greater greater than 80 percent sensitivity and greater than 90 percent specificity in detection of adeno- and small cell CA; toward squamous cell CA only SPIA-T, which is readily performed quantitatively and repeatedly, had such sensitivity. We want to distinguish early CA from nonmalignant and borderline lesions, and monitor the effect of therapy on CA. We intend to establish a rapid, economic assay for diagnosis of and possibly screening for CA. We will focus on early detection and on monitoring for recurrences. We are developing 2 in vitro tests to measure CMI to T, to circumvent the inconveniences of the delayed-type hypersensitivity skin test. We will extend successful attempts by others and by us to relate density of T receptors on CA cells with aggressiveness, and also that of Tn receptors. Satisfactory (early) diagnosis of CA requires precise localization of minute CA in addition to detection. We plan to establish firmly our preliminary work with human [131I]- anti-T IgG to localize T-active TA3 mouse mammary adenoCA metastases by external scanning in a step towards pinpointing early human CA and metastases. Implications of our work may be far-reaching, as we and others have indications that we measure a dynamic interaction of the cancer patient's immune system with the T-specific structures of the tumor.
