Antibodies and Soluble Tumour-specific Antigens in Blood and Lymph of Rats with Chemically Induced Sarcomata

Abstract

Summary.-In confirmation of other studies it has been shown that antibody directed against the tumour specific transplantation-type antigens (TSTAs) cannot be detected in rats with a tumour growing intramuscularly but appears within a few days after excision of the tumour. Circulating antibody is found in the serum of rats with lymph node metastasis following excision of the primary. Absorption by the intramuscular tumour of circulating antibody does not account for the absence of antibody since the antibody levels in thoracic duct lymph in rats with tumours in the leg are also very low and rise rapidly after tumour excision. Antibody is released by the draining nodes directly into the lymph and must pass through the thoracic duct before entering the blood. Under these conditions low levels of antibody activity in lymph cannot be ascribed to absorption by the tumour.It is postulated that TSTA is released from the tumour into the lymph. Following injection of tumour cells into immunized rats the level of antibody falls and this is attributed to release of TSTA from the injected cells. The possible role of antigen release from tumours in determining the host reaction to the tumour is discussed.ANTIBODIES to tumour-specific trans-70we decided to test whether absorption of plantation antigens (TSTA) of chemically-antibodies by the tumour occurred by induced sarcomata in rodents are present determining the antibody levels in the in serum after excision of the tumour but thoracic duct lymph of rats with tumours cannot be detected while growing tumour in the leg. is present (Pilch and Riggins, 1966; The nodes draining such tumours are Harder and McKhann, 1968; Thomson, highly stimulated (Alexander et al., 1969) Steele and Alexander, 1973; Baldwin, and contain many plasma cells. Their Embleton and Robins, 1973). The expla-efferent lymph, which would be expected nation has been advanced that this to contain antibodies, is discharged phenomenon-is due to absorption of the directly into the thoracic duct before circulating antibody by the tumour reaching the tumour. Therefore, should (Harder and McKhann, 1968; Ran and the absence of antibodies in the blood of Witz, 1970; Buchsbaum, 1972). If tumour-bearing animals be due to absorpabsorption were, in fact, the principal tion by the tumour, then antibodies mechanism, one would expect the tumour should be detected in moderate to high cells to be covered with antibodies. Our concentration in the thoracic duct lymph experiments failed to show antibodies of such animals. However, in the study bound to the cell surface of tumours to be reported here measurable antibody growing in vivo. However, such a nega-levels in the lymph are very low while the tive finding is not conclusive. Therefore tumour is in situ and rise when the

Radioimmunoassay of Tumour Specific Transplantation Antigen of a Chemically Induced Rat Sarcoma: Circulating Soluble Tumour Antigen in Tumour Bearers

“…0-3 ml of the " antigen fraction" derived from 2 ml of a serum or 5 ml of a lymph sample were assayed. Thoracic duct cannulation, collection and preparation of lymph were as previously described (Thomson, Eccles and Alexander 1973c).…”

“…Sjogren et al (1971) have postulated that TSTA complexed with specific antibody may constitute the " blocking " material described by Hellstr6m et al (1971) in the serum of cancer patients. As already indicated, specific antibody is produced during tumour growth (Thomson et al, 1973c) and this antibody complexes with soluble circulating antigen (Thomson et al, 1973b). Moreover, no evidence was obtained to indicate that tumour cells in situ are coated with significant quantities of antibody (Thomson et al, 1973c).…”

“…In earlier studies it was found that antibodies directed to the TSTA of chemically induced sarcomata could not be found in the serum of tumour bearing rats, whereas after removal of tumour by amputation of the leg, anti-TSTA antibodies could be detected in the serum by membrane immunofluorescence and by mixed haemabsorption (Thomson et al, 1973c). The most simple explanation, that the antibody was absorbed in vivo by the tumour, was shown not to be an 385 important factor by measuring specific antibody in the thoracic duct lymph to the TSTA of sarcomata growing in the leg.…”

“…On the membranes of chemically induced tumours of rats and in early embryos a common tumour associated antigen was previously detected by membrane immunofluorescence with syngeneic tumour immune serum and it was termed " OEAI " (Thomson and (Thomson et al, 1969) and the normal HL-A antigens (van Rood, van Leuven and van Santen, 1970). In earlier studies it was found that antibodies directed to the TSTA of chemically induced sarcomata could not be found in the serum of tumour bearing rats, whereas after removal of tumour by amputation of the leg, anti-TSTA antibodies could be detected in the serum by membrane immunofluorescence and by mixed haemabsorption (Thomson et al, 1973c).…”

Blocking factors against leucocyte-dependent melanoma antibody in the sera of melanoma patients

“…Serum factors having this activity have been demonstrated in both animal (Hellstr6m and Hellstrim, 1969;Sjogren, 1971, 1973;Robins, 1972, 1973;Thompson, Eccles and Alexander, 1973) and human studies (Hellstrom et al, 1971;Currie and Basham, 1972;Baldwin, Embleton and Price, 1973;Jose and Seshadri, 1974). In particular, studies on melanoma subjects appear to confirm the importance of these factors by demonstrating a good correlation between the presence of blocking factors of CMC in the sera of melanoma patients and the clinical course of tumour growth (Hellstrom and Hellstr6m, 1973;Hellstrom et al, 1973).…”