Potentiation of therapeutic effect of recombinant tumour necrosis factor against B16 mouse melanoma by combination with recombinant interleukin 2

Matsuyama

Experimental Dermatology

et al. 1995

Self Cite

To determine the therapeutic mechanism of PUVA in psoriasis vulgaris, the effects of PUVA on activated T lymphocytes were investigated in vitro. Peripheral blood mononuclear cells (PBMC) obtained from healthy volunteers were activated with Con A stimulation (Con A blasts). Both untreated PBMC and Con A blasts were irradiated with UVA light in the presence of 8-methoxypsoralen (8-MOP). The expressions of CD4, CD8, VLA-4 and LFA-1 of PBMC and Con A blasts were stained with each monoclonal antibody and the intensity of fluorescence was analyzed by FACScan. PUVA-treated PBMC showed decreased response to both Con A and PHA stimulation. PUVA treatment also suppressed the IL-2 production of Con A blasts and IL-2 response of PBMC with increasing UVA fluence. The expressions of LFA-1, VLA-4, CD4, CD8 and CD25 (IL-2R) molecules were decreased in PUVA-treated Con A blasts. Con A blasts were more sensitive than untreated PBMC to PUVA treatment. These results suggest that the therapeutic effects of PUVA on psoriasis vulgaris can be induced by suppression of the expression of cell surface molecules of activated T lymphocytes.

Section: Il-2 Productionmentioning

confidence: 99%

PUVA suppresses the expression of cell adhesion molecules of lymphocytes

Matsuyama

Experimental Dermatology

et al. 1995

Self Cite

Cytokines as Vaccine Adjuvants

Dong

Brunn

1995

Vaccine Design

This paper describes the bacterial expression and purification of bioactive recombinant ovine interleukin-2 (rovIL-2), interleukin-la (rovlL-la) and tumour necrosis factor a. These purified proteins had specific activities in appropriate bioassays of 1x10^, 1 x lO' and 1x10^ U/mg, respectively. Recombinant ovIL-la was assessed as an immunological adjuvant for the sheep response to the model protein avidin. Wben delivered either intradermally or intramuscularly in conjunction with avidin in aluminium hydroxide the rovIL-la significantly enhanced the secondary humoral response. Doses of 1, 10 or 100 |ig per sheep enhanced the humoral response to a similar extent. Recombinant ovIL-ip had similar adjuvant activity in that it was demonstrated to significantly enhance the sheep humoral response to an experimental H. contortus antigen. This increase in specific antibody, however, did not correlate with enhanced protection against infection with third stage H. contortus larvae. In addition incorporation of rovIL-1 P into the formulation was shown not to alter the isotype profile of H. contortus antigen specific antibody.

Cancer Chemother. Pharmacol.

Comparison of the antitumor activity of bryostatins 1, 5, and 8

Kraft

Woodley

Pettit

et al. 1995

Bryostatin 1, a macrocyclic natural lactone isolated from a marine Bryozoan, has undergone phase I testing in humans. Side effects of treatment have included muscle pain and joint aches, a transient decrease in platelets, and the release of tumor necrosis factor alpha (TNF alpha) and IL-6 into the blood stream. In animals, anticancer activity has been demonstrated against murine leukemias, lymphomas, melanomas, and sarcomas. The mechanism of action of this compound depends in part on its ability to activate protein kinase C. To determine the biologic activity and toxicity of other members of the family of bryostatin compounds, we studied the ability of bryostatins 5 and 8 to inhibit the growth of murine melanoma K1735-M2. Bryostatins 1, 5, and 8 induced equivalent inhibition of melanoma growth, but bryostatins 5 and 8 induced less weight loss than bryostatin 1 (P < 0.001). Neither the injection of an antimurine TNF alpha antibody nor an adenovirus, which produces a mutated TNF receptor inhibiting TNF alpha activity, into mice had any effect on either bryostatin-induced weight loss or melanoma tumor growth inhibition. Using a novel competition assay, the levels of bryostatin in the plasma were measured. The approximate half-life (t1/2) of bryostatin was 8.62 min, the clearance (Cl) 3.53 ml/min and the AUC 322.20 nmol/l min. A similar result was obtained with each bryostatin analog. These results suggest that human testing of additional bryostatin analogs may yield compounds with similar antitumor activity but decreased side effects. A novel assay to measure the level of all bryostatins in the plasma of patients undergoing treatment is described.