Alan S. MacDonald

Immunochemotherapy of human malignant melanoma with chlorambucil-carrying antibody

Abstract Heterologous anti-melanoma sera produced against any one patients tumour cross-react, to varying degrees, with both the cytoplasmic and surface antigens of melanoma cells from other patients. Intravenous injections of cross-reacting antimelanoma antibodies bound to chlorambucil were followed by the regression of a considerable number of skin metastases in a patient with disseminated malignant melanoma. When immunochemotherapy had to be discontinued because of anaphylaxis, many of the metastases which had almost completely regressed, reappeared and grew progressively in spite of chemotherapy. One metastatic nodule which had not regressed and another which appeared during immunochemotherapy contained a much larger proportion of tumour cells lacking the cross-reacting surface antigen, when compared to tumour cells in metastatic nodules excised before immunochemotherapy.

Failure to Correct the Metabolic Defect by Renal Allotransplantation in Fabry's Disease

Plasma neutral glycolipid levels and plasma and leukocyte alpha-galactosidase activities were measured serially before and after renal allotransplantation in two men, aged 47 and 45 years, with renal failure due to Fabrys disease. The patients were followed posttransplantation for 92 and 64 weeks, respectively. No significant elevation of plasma or leukocyte alpha-galactosidase activities above levels in untreated men with Fabrys disease or decrease in the levels of trihexosyl ceramide was observed in either patient. The results do not support the use of renal allotransplantation for enzyme replacement in Fabrys disease.

Antibody as carrier of 131I in cancer diagnosis and treatment

Cell‐surface localizing heterologous antibodies against mouse EL4 lymphoma, Ehrlich ascites carcinoma, and several human malignant tumors could be bound to varying amounts of131I without interfering with the reactivity of these antibodies with their respective tumor cells. Exposure of the mouse tumor cells to radio‐iodinated antitumor antibodies in vitro, or the injection of radioiodinated antitumor antibodies into mice preinoculated with tumor cells resulted in either partial or complete tumor inhibition depending upon the amount of 131I activity carried by the antibodies. Injecten of comparable amounts of the immunoglobulin alone or of 131I bound to normal globulin did not cause any tumor inhibition. Intraperitoneally injected radio‐iodinated anti‐EL4 antibody was found to localize preferentially in the subcutaneous transplants of EL4 lymphoma. Similar localization of intravenously injected radio‐iodinated antibodies was observed in the metastases of two cancer patients.

Radionuclide imaging of metastases from renal-cell carcinoma by 131I-labeled antitumor antibody.

On immunofluorescence assay, goat antisera reacted with renal-cell carcinomas from 20 patients, but not with adult normal human tissues (including patients normal kidney). After in travenous injection, the 131I-labeled antibody localized preferentially in metastatic renal carcinoma in 6 consecutive patients. Labeled antitumor antibodies may have the specificity for tumor imagining which current radiopharmaceuticals lack.

Repeat Cadaver Kidney Transplantation Using Cyclosporine a Immunosuppression

Repeat cadaver kidney transplantation using azathioprine immunosuppression carried a higher risk of graft loss than primary transplants. We analyzed the results of repeat cadaver kidney grafting with cyclosporine A immunosuppression. A total of 33 cyclosporine A-treated patients received the second kidney transplant at varying intervals after failure of the first transplant. Graft survival at 1 year was 66 per cent. A concurrent group of 189 cyclosporine A-treated first cadaver kidney recipients had a 1-year graft survival rate of 75 per cent, although this better result was not statistically significant (p greater than or equal to 0.25). A historical group of 31 azathioprine-treated second graft recipients had a significantly worse 1-year graft survival rate of 45 per cent compared to the cyclosporine A second graft group (p less than 0.1). Patient age, sex, early first graft loss, interval between transplants and the presence of panel reactive antibodies were not factors in predicting second graft outcome. A complete DR mismatch appeared to worsen the second transplant survival. These findings indicate that early graft survival of cyclosporine A-treated repeat cadaveric transplants is acceptable and is better than azathioprine-treated first or second grafts.