Aberrant glycosylation is a hallmark of
cancer cells. The
blood group precursors T (Thomsen-Friedenreich) and Tn
epitopes are shielded in healthy and benign-diseased tissues but uncovered in approx. 90% of
carcinomas. T and Tn
glycoproteins are specific, autoimmunogenic pancarcinoma
antigens. These
antigens may also be found in neoplastic blood cells (and on LTV-II infected T lymphocytes). Fundamental chemical and physical aspects of these
glycoproteins of primary
carcinomas are discussed first. Tn and T
epitopes are cell and
tissue adhesion molecules, essential in invasion by and
metastasis of
carcinoma which includes adherent and proliferative phases. These properties are then delineated next, followed by consideration of pathophysiological and clinical aspects of these
antigens. Immunohistochemical studies of the extent of
Tn antigen expression in primary
breast carcinoma demonstrate it highly significant correlation with clinicopathological
tumor stages, and hence its value as a reliable prognosticator. On the other hand, there is no significant, prognostically useful association between
T antigen expression and clinical disease course. Everyone has "preexisting" anticarcinoma anti-Tn and
anti-T antibodies, induced predominantly by the intestinal flora, while cellular immune responses to T and Tn
epitopes are evoked only by
carcinomas and some
lymphomas.
Carcinoma dedifferentiation leading to predominance of Tn over T
epitopes is described, as is the role of Tn and T
epitopes in very early, including preclinical,
carcinoma detection. The highest sensitivities in
carcinoma detection are for preclinical and the earliest clinical stages. Obviously, preclinical
carcinoma detection is of practical importance. T/
anti-T tests detected preclinical
carcinoma in 77% of 48 patients long (mean 6 years) before their biopsy/X-ray results became positive. There were no false predictions of
carcinoma in 38 control persons with benign diseases (observation average 4.8 years). These findings open a novel window for both curative approaches and pathophysiological studies. The autoimmunogenicity of
carcinoma T/
Tn antigen led us more than two decades ago to begin intradermal vaccination of patients with advanced
breast carcinoma of stages IV-IIb, predominately after
modified radical mastectomy and sometimes
lumpectomy plus axillary dissection always followed by adjuvant radio/
chemotherapy. The
vaccine consists of human group O red blood cell membrane derived, HLA-free T/
Tn antigen containing as adjuvant
Ca3(PO4)2 plus a trace of phosphoglycolipid A hyperantigen, i.e., S typhi
vaccine (USP), which itself has T and Tn specificities. Our efforts have now for up to 20 years remained successful in a large majority of the 32 patients. All 32 patients survived at least 5 years; 10-year survival was statistically highly significantly improved (5-year survival: P < 1 x 10(-7); 10-year survival: P < 1 x 10(-5)) compared to statistics of the United States National Cancer Institute. Because these vaccinations are successful, their extension to large populations with major types of
carcinomas should be considered, and even immunological
carcinoma prevention may be contemplated.