Use of tumor-infiltrating lymphocytes and interleukin-2 in the immunotherapy of patients with metastatic melanoma. A preliminary report.

Lymphocytes extracted from freshly resected melanomas can be expanded in vitro and can often mediate specific lysis of autologous tumor cells but not allogeneic tumor or autologous normal cells. We treated 20 patients with metastatic melanoma by means of adoptive transfer of these tumor-infiltrating lymphocytes and interleukin-2, after the patients had received a single intravenous dose of cyclophosphamide. Objective regression of the cancer was observed in 9 of 15 patients (60 percent) who had not previously been treated with interleukin-2 and in 2 of 5 patients (40 percent) in whom previous therapy with interleukin-2 had failed. Regression of cancer occurred in the lungs, liver, bone, skin, and subcutaneous sites and lasted from 2 to more than 13 months. Toxic effects of interleukin-2 occurred, although the treatment course was short (five days); these side effects were reversible. It appears that in patients with metastatic melanoma, this experimental treatment regimen can produce higher response rates than those achieved with interleukin-2 administered alone or with lymphokine-activated killer cells. It is too early to determine whether this new form of immunotherapy can improve survival, but further trials seem warranted.

The application of enzyme-linked immunosorbent assays (ELISA) to neuropeptides.

Procedures are presented for routine evaluation of antibody specificity, titre, and quantitation of antigen levels in tissue extracts without the use of radiolabeled probes. A colorimetric, enzyme-linked immunosorbent assay (ELISA) is described for general use with neuropeptides, using neurotensin as a primary example. These assays use rabbit anti-neurotensin immune serum which is colorimetrically identified after combination with an alkaline phosphatase-conjugated, affinity purified, goat anti-rabbit IgG and reaction with the chromogenic substrate, p-nitrophenyl phosphate. Because the principle of these methods can be adapted for use with various proteins and neuropeptides, they should find widespread applicability in neurobiology.

Features independent of stain intensity for evaluating Feulgen-stained cells.

Eleven features that are independent of stain intensity are described. Values greater than 1.4 times the average optical density were shown to define the visually darker areas of the image, which were considered to be condensed chromatin. Use of the 11 features permitted the discrimination between (1) lymphocytes and macrophages of rats, (2) macrophages from the spleens of rats and monocytes from peripheral blood and (3) macrophages from the spleens of rats injected with complete Freund's adjuvant and those from the spleens of normal rats.

Viral events necessary for the induction of interferon in chick embryo cells.

Temperature-sensitive mutants of Sindbis virus were employed to investigate the nature of the viral event(s) which induces chick-embryo cells to produce interferon. Chick embryo cells induced by the parental heat-resistant strain of Sindbis virus produced essentially equal amounts of interferon at 29 and 42 C. An RNA(-) and three RNA(+) strains [temperature-sensitive mutants unable (RNA(-)) and able (RNA(+)) to make ribonucleic acid] produced interferon at 29 C but not at 42 C. It is concluded that viral RNA per se and the replication of viral RNA do not induce interferon production by chick embryo cells.