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H F Dullens

Publications and source records attributed to H F Dullens.

68 records · Page 4Linked to original sources

Influence of whole body irradiation on intraperitoneal immunity in a syngeneic mouse lymphoma system.

DBA/2 mice were immunized against the syngeneic SL2 lymphoma by two injections with irradiated lymphoma cells or by two injections with irradiated cells followed by one injection with unirradiated cells. Whole body irradiation (500 rad) of the immunized mice caused a significant decrease in the number of peritoneal macrophages and lymphocytes. The spleen weight showed a transient decrease. However, whole body irradiation did not cause a significant decrease of the survival time of immunized mice challenged intraperitoneally with SL2 lymphoma cells.

Animals↗

Therapy with antibody-coated immune and hyperimmune peritoneal cells in a murine lymphoma system.

Goat-antimouse (DBA/2) SL2 lymphoma immunoglobulin was specifically cytotoxic to DBA/2-derived sl2 lymphoma cells. This anti-SL2 immunoglobulin, or a part of it, was cytophylic for peritoneal macrophages as shown by target cells adhering to macrophages incubated in vitro with the immunoglobulin. The target cells became free in the medium after incubation with 0.1% trypsin for 1 hour. In in vivo experiments, the incubation of immune or hyperimmune peritoneal cells with immunoglobulin from normal goat serum or from goat-anti-SL2 serum before use in immunotherapy decreased the number of DBA/2 mice surviving for more than 35 days an intraperitoneal injection with SL2 cells compared to the number of survivors inoculated with immune or hyperimmune cells only. These results show that, in immunotherapy with immune cells, we must consider the possibility that specific antitumor antibodies and antibodies not directed against the tumor cloud the therapeutic potnecy of the immune cells.

Adsorption↗

Effective immunotherapy with local low doses of interleukin-2.

IL-2 treatment for metastatic tumors in man is usually given systemically with high doses, often in conjunction with large numbers of LAK-cells. Complete tumor regression is obtained in less than 10%, this treatment causes severe toxicity, and culturing of LAK-cells is laborious and expensive. In this paper we demonstrate that small amounts of locally applied rIL-2 alone, if given at the right time, can cure about 70% of DBA/2 mice with large metastasized syngeneic SL2 lymphoma comprising 4-10% of the total body weight, a tumor load hitherto considered fatal. Moreover, 3 out of 5 cows with ocular squamous cell carcinoma (BOSCC) of 1 x 1 up to 3 x 4 cm were cured with low doses of rIL-2 only. Taken together, we have now tested 11 tumors in animals. No antitumor effect was observed in EL4 lymphoma in C57BL mice. Partial antitumor effects were detected in RBL5 lymphoma in C57BL mice, stomach carcinoma in BALB/c mice, MOT-carcinoma in C3H mice, liver carcinoma in guinea pigs and bovine vulval papilloma/carcinoma. Complete tumor regression was obtained in SL2 lymphoma, L5178Y lymphoma, L1210 lymphoma, and P815 mastocytoma in DBA/2 mice and in bovine ocular squamous cell carcinoma. Low doses of locally injected IL-2 induce systemic immunity, as shown in DBA/2 mice bearing syngeneic SL2 lymphoma cells. We conclude that local low dose treatment can be effective and results in a high cure rate in several tumor models. In the DBA/2-SL2 lymphoma model this treatment is 100-1000 times more effective than any form of immunotherapy we have tested during 20 years in this model.(ABSTRACT TRUNCATED AT 250 WORDS)

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Cancer treatment with interleukins 1, 4 and 6 and combinations of cytokines: a review.

During the last few years the anticancer effects of recombinant cytokines has been studied in animal experiments and in clinical trials. Significant anticancer effects of especially, interleukin-2 (IL-2) and interferon alpha (IFN alpha) have been obtained. In this paper, we shall focus on the studies and possible applications of interleukin 1 (IL-1), interleukin 4 (IL-4), interleukin 6 (IL-6) as single agents and focus on some combinations of cytokines. Finally, we shall discuss future developments that can be expected.

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Mechanisms of tumor regression induced by low doses of interleukin-2.

We have demonstrated that local treatment with low doses of IL-2 can cure mice bearing a large burden of metastasized SL2 lymphoma. Different mechanisms lead to rejection of ascitic SL2 tumor and solid s.c. SL2 tumor. For local rejection of ascitic tumor cytotoxic T-lymphocytes were essential, whereas the cytotoxic activity of macrophages was also important for tumor rejection. In distant solid tumors very few infiltrating lymphocytes and macrophages were present. Nevertheless, IL-2 treatment rapidly induced necrosis that seemed to be caused by stasis of blood flow in the tumors. This may be mediated by the local release of cytokines like TNF. We conclude that both cytotoxic activity and the production of cytokines by T-cells is essential for IL-2 induced systemic tumor rejection.

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Tumour regression by IL-2 mediated stagnation of blood flow.

The histology of Interleukin-2 induced tumour regression is presented. DBA/2 mice were injected simultaneously ip (intraperitoneally) and sc (subcutaneously) with 2 x 10(4) and 2 x 10(5) syngeneic SL2 lymphosarcoma cells, respectively. After treatment with 20,000 U IL-2 given ip at days 10-14, 50% of these mice survive. Histological analysis of the sc tumours showed that stagnation of blood flow and an occurrence of sudden massive necrosis were indicative of tumour regression. We hypothesize that peritoneal lymphocytes, activated by the ip tumour cells and IL-2, home in the sc tumour. There these activated lymphocytes produce lymphokines and trigger off other infiltrate cells to do similarly. This causes vascular leakage which leads to an increased intratumoural interstitial hydrostatic pressure. Subsequently circulatory obstruction and tumour necrosis occurs.

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The glycosylation profile of interleukin-2 activated human lymphocytes correlates to their anti-tumor activity.

BACKGROUND: Natural killer cells display spontaneous, non-MHC-restricted cytotoxicity against tumour cells, which is strongly enhanced after incubation with IL-2. The molecular background of the increased anti-tumour activity of these lymphokine-activated killer cells is still only partly understood. MATERIALS AND METHODS: In this paper, investigation has been made of the correlation between cell surface glycosylation and anti-tumour activity of LAK cells by stimulating peripheral blood lymphocytes with interleukin-2, in the presence of inhibitors of N- and O-glycosylation. RESULTS: Inhibition of N- or O-glycosylation of proteins during IL-2 activation leads to a 70-80% decrease in the cytolytic activity of LAK cells against K562 and Daudi tumour cells, coinciding with drastic alterations in their cell surface carbohydrate profile. CONCLUSION: The conclusion is drawn that there is a clear correlation between the glycosylation of LAK cell glycoproteins and their anti-tumour activity which points to the involvement of cell surface glycoconjugates in the development of LAK activity.

1-Deoxynojirimycin↗