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

Summary.-The tumour specific transplantation antigen (TSTA) from a chemically induced rat sarcoma has been isolated as an electrophoretically homogeneous soluble material by affinity chromatography using a Sepharose bound antibody raised to the tumour in syngeneic rats. The TSTA is specific for the particular tumour used (the MC-1 sarcoma) and does not cross-react with material extracted from other rat sarcomata. In addition, a material with different physicochemical properties which cross-reacted with different sarcomata was also eluted from the antibody column and this may be the previously identified onco-embryonic antigen (OEAl) which is immunogenic in the syngeneic host.The purified TSTA labelled with 125I was used in a radioimmunoassay which detected soluble TSTA in rats bearing a MC-1 sarcoma. The assay shows that tumour transplantation is associated with a persisting release of soluble antigen into the circulation. This antigenic burden is present continuously and renewed as long as the tumour mass exists.

Summary Lymph node status is still the single most important prognostic factor in breast cancer. Axillary surgery remains the only reliable means of providing this information. This pilot study evaluates using a highly specific radiolabelled monoclonal antibody to provide equivalent infornation by a non-invasive technique.After optimisation of labelling conditions, our first antibody, ICR12 (against the gene product of c-erbB-2) was evaluated in a mouse model system. Twenty-four hours post i.v. injection the mice were killed and their organs, blood and tumours harvested for counting. Tumour localisation was four times greater than that into normal tissues, reaching 20% injected dose per gram of tumour.Eight patients have had this Tc99m-ICR12. Patient selection was by immunocytochemical staining of fine needle aspirates from the patient's own breast cancer. After intravenous administration of the immunoconjugate, tomographic images were obtained at 24h. These results were compared to the subsequent histopathological examinations. Three patients acted as normal controls, one patient was negative due to inappropriate sampling, and two patients had strong membrane staining and provided excellent tumour localisation to both breast primary and regional node metastases. A further two patients only had moderate antigen expression on staining and did not localise well.The good performance of this radiolabelled antibody with patients that strongly stain for the antigen encourages the development of this system as both a method of staging breast cancer and a potential means of immunotherapy in this subgroup of patients.

Summary.-Animals bearing metastatic fibrosarcomas were treated with cyclophosphamide (CY) alone or in combination with flurbiprofen (FP), an inhibitor of prostaglandin synthesis. FP did not affect local growth of fibrosarcomas, and the incidence of distant metastases after resection of the "primary" implants was comparable in treated and control groups. Treatment with CY retarded growth of the fibrosarcomas and reduced the proportion of animals which succumbed to metastases, but this was not altered significantly by additional treatment with FP. FP did not affect the survival of rats bearing a lymphoid leukaemia. The lifespan of animals treated with CY was increased significantly, but the concomitant administration of FP did not enhance this effect.

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