ISSN:0732-6580    

出版商:OVID    

年代:1985

数据来源: OVID

ISSN:0732-6580    

出版商:OVID    

年代:1985

数据来源: OVID

摘要:

Summary:Human leukocyte interferon, HuIFN‐&agr;(Le), has been tested in combination with radiotherapy and chemotherapy for previously untreated small cell lung cancer. Nine patients with limited disease received high‐dose IFN followed by a low‐dose regimen; and six patients had a low‐dose regimen from the beginning. The high dosage of IFN consisted of 800 × 106IU given as a continuous intravenous infusion for 5 days, followed by 6 × 106IU i.m. three times weekly. If the first site of disease progression was local or in a central nervous system location, radiotherapy (55 Gy/20 F/7 weeks locally and/or 30 Gy/10 F/2 weeks whole brain) was applied and IFN was continued. Chemotherapy was administered only if there was disease dissemination outside the chest. Three patients achieved minor response for as long as 20, 25, and 42 weeks, respectively, with IFN alone. Three of five complete responders to IFN‐radiotherapy died 18, 33, and 41 weeks from the start of IFN treatment without chemotherapy. Autopsy did not reveal macroscopic or microscopic tumor at any site, but there was severe radiation pneumonitis. Four of nine patients were administered chemotherapy subsequent to IFN‐radiotherapy because of disease dissemination. The median length of survival of the entire group was 41 weeks. On the low‐dose regimen, one patient achieved partial response with IFN alone (duration, 12 weeks); of five evaluable patients three achieved complete remission and two partial remission to IFN‐radiotherapy, and one of the three complete responders to IFN‐radiotherapy died of severe radiation pneumonitis at 21 weeks from the start of IFN treatment. No tumor was detected at autopsy. The study is in progress. Average survival at present is 33 weeks. The results derived from both our studies suggest a growth‐delaying effect of HuIFN‐&agr;(Le) on small cell lung cancer. They also suggest potentiation of radiation by HuIFN‐&agr;(Le). Memory and psychomotor dysfunction, fatigue, and anorexia were dose limiting with both short‐duration, high‐dose and long‐duration, low‐dose IFN therapy. We feel that IFN, as part of a combined multimodality treatment of small cell lung cancer, may play a role by delaying metastatic dissemination.

ISSN:0732-6580    

出版商:OVID    

年代:1985

数据来源: OVID

摘要:

Summary:We report that recombinant human interleukin‐2 (rhIL‐2) can support the growth of murine IL‐2‐dependent cytotoxic T lymphocyte cell lines, augment mouse natural killer (NK) cell activity in vitro, and, as a sole stimulus, induce and maintain the proliferation of mouse lymphocytes. rhIL‐2 also augmented mouse allogeneic mixed lymphocyte response and enhanced the development of alloreactive cytotoxic T cells in vitro. The intraperitoneal injection of rhIL‐2 augmented peritoneal NK cell activity, whereas splenic NK cell augmentation required significantly higher levels of rIL‐2. Thus, rhIL‐2 is able to augment both NK cell activity in vitro and in vivo and T cell activity in vitro. These results suggest that rhIL‐2 has clinical therapeutic potential since it is able to induce multiple lymphocyte functions and activities. Because rhIL‐2 is highly effective for mouse cells, preclinical model systems can be readily developed that will allow us to explore the conditions needed for optimal therapeutic efficacy. Owing to the lymphocyte stimulatory nature of the rhIL‐2, the monitoring of hemopoietic and leukocyte parameters during clinical rhIL‐2 trials will be critical.

ISSN:0732-6580    

出版商:OVID    

年代:1985

数据来源: OVID

摘要:

Summary:The lymphokine interleukin‐2 (IL‐2) has been shown to enhance natural cell‐mediated cytotoxicity, the generation of cytolytic T lymphocytes, and several other aspects of cellular immune function. The gene coding for human IL‐2 has been cloned, and recombinant IL‐2 will be available for clinical trials in patients with neoplastic, infectious, and immunodeficiency diseases. The present investigation was undertaken to determine if IL‐2 was similar to interleukin‐1 (IL‐1) in its ability to induce fever and the acute‐phase response. These studies were based on recent work with recombinant human interferon (IFN)‐&agr;, which is intrinsically pyrogenic and capable of producing fever by inducing the synthesis of prostaglandin E2(PGE2). The prospect that IL‐2 might exert similar physiologic effects is of critical concern since elevated temperature, PGE2, and acute‐phase reactants may profoundly inhibit natural cell‐mediated cytotoxicity. Our studies have shown that recombinant human IL‐2 is not intrinsically pyrogenic in rabbits at doses as high as 10,000 units/kg when administered by a single intravenous injection. In contrast to IL‐1, IL‐2 does not stimulate cultured hypothalamus cells to synthesize PGE2, and, furthermore, IL‐2 does not elevate serum C‐reactive protein levels. These results predict that the administration of IL‐2 to patients in doses that stimulate cellular immune function will not induce fever and other toxic side effects frequently seen in individuals receiving IFN.

ISSN:0732-6580    

出版商:OVID    

年代:1985

数据来源: OVID

摘要:

Summary:Peritoneal macrophages (PM&thgr;) from mice treated intraperitoneally with the unique polyanionic compounds cyclohexyl‐1,3‐dioxepin maleic anhydride copolymer (CDA‐MA) and 4‐methyl‐2‐pentenoyl maleic anhydride copolymer (MP‐MA) had tumoricidal activity against Lewis lung tumor cells. 5′‐Nucleotidase ectoenzyme activity, which had previously been associated only with nontumoricidal, resident PM&thgr;, was elevated in tumoricidal PM&thgr; elicited with CDA‐MA and MP‐MA. Cell counts and differentials performed on peripheral blood leukocytes and PM&thgr; populations from CDA‐MA‐ and MP‐MA‐treated mice more closely corresponded to those of normal mice than mice treated with the conventional PM&thgr;‐activating agents pyran andCorynebacterium parvum.In addition, the lysosomal peroxidase activity in PM&thgr; after administration of CDA‐MA and MP‐MA remained at levels comparable with normal resident PM&thgr;, while an influx of peroxidase‐positive macrophages was observed after administration of pyran andC. parvum.Inoculation of CDA‐MA and MP‐MA into mice bearing Lewis lung carcinoma showed a significant increase in median survival time compared with control mice, as well as an increase in the percentage of mice that survived >90 days. Taken together, these data suggest that CDA‐MA and MP‐MA activated PM&thgr; in situ and prolonged survival against primary transplanted Lewis lung carcinoma.

ISSN:0732-6580    

出版商:OVID    

年代:1985

数据来源: OVID

摘要:

Summary:Interferon (IFN) caused the transfer of natural cytotoxic activity between human leukocytes in a syngeneic system. The transfer of cytotoxic activity was found to be dependent on the cell density and was in proportion to the IFN concentration. Human immune‐type IFN (IFN‐&ggr;) was more efficient than IFN‐&agr; or IFN‐&bgr; in eliciting the transfer of cytotoxic activity. The transfer occurred with IFN‐&ggr; preparations of various specific activities and with recombinant IFN‐&ggr;. The transferred activity had the characteristics of an IFN‐induced antiviral state, in that it was blocked either by actinomycin D or by prevention of cell contact. Specific antibodies to IFN had no effect on the transfer of cytotoxic activity. Protection of mouse target cells from human cytotoxic activity could also be transferred from IFN‐induced human foreskin fibroblasts (HFF) insensitive to cytotoxic activity to the cytotoxic‐sensitive mouse cells. The transfer of protection was highly efficient at ratios of one HFF cell to 16 mouse target cells. The transfer of cytotoxic activity, and protection from cytotoxic activity, may represent a mechanism for amplification of the IFN system as a host defense against viralinfected or tumor cells.

ISSN:0732-6580    

出版商:OVID    

年代:1985

数据来源: OVID

摘要:

Summary:Six immunomodifier drugs have been studied with regard to their capacity for decreasing radiation‐induced effects on lymphocytes. The T cell colony method was selected for this evaluation because this technique takes into account reproductive integrity of the lymphocyte. Irradiation was delivered either in vitro to murine splenocytes or in vivo (total body) at 0.75 Gy, a dose close to the D37calculated for lymphocyte survival, using the same technique. Among immunomodifiers, only the drugs known for their specific action on ionizing radiation effects (quenching of free radicals) were shown capable of radiorestoration: this is essentially true for retinoic acid—even more than for its derivative—which restored the T cell colony formation up to 80% of the control at 10‐6Mfinal concentration in vitro. However, when given in vivo to irradiated mice, retinoic acid is active only at high doses.

ISSN:0732-6580    

出版商:OVID    

年代:1985

数据来源: OVID

摘要:

Summary:Proliferation of normal human T cells in vitro requires activation of resting T cells by lectin or antigen. This stimulation initiates a series of events which includes elaboration of T cell growth factor (TCGF), expression of TCGF receptors, and, ultimately, cellular proliferation. We sought to determine if TCGF was required for expression of the TCGF receptor in phytohemagglutinin (PHA)‐stimulated normal human T cells. Utilizing dexamethasone (DEX), a known inhibitor of TCGF production, reductions in T cell proliferation, TCGF production, and TCGF receptor expression, as measured by TCGF adsorption and Tac acquisition, were demonstrated after PHA stimulation. When exogenous partially purified TCGF was added to DEX‐containing cultures, the DEX inhibition of proliferation and TCGF receptor expression was completely reversed. These experiments were reproduced utilizing both highly purified TCGF from the Jurkat cell line and purified TCGF synthesized by bacteria from cloned TCGF DNA. Short‐term experiments showed TCGF to be capable of restoring Tac antigen expression after DEX inhibition in the absence of cellular proliferation. These results indicate that TCGF is required for optimal expression of Tac antigen—associated TCGF receptors in PHA‐activated T cells.

ISSN:0732-6580    

出版商:OVID    

年代:1985

数据来源: OVID

摘要:

Summary:Human interleukin‐2 proteins (IL‐2), purified to homogeneity from both the Jurkat cell line and from genetically engineeredEscherichia coli, were compared in a variety of biological systems. The gene coding for the recombinant IL‐2 protein used in these studies contained a site‐specific modification resulting in the replacement of a cysteine residue with a serine residue at position 125 in the encoded polypeptide. The specific activity was 2‐4 × 106units/mg for both the recombinant IL‐2125and the native IL‐2 molecules when measured by DNA synthesis in the murine HT2 cell line. The abilities of these two molecules to support the short‐term proliferation and the long‐term growth of mitogen‐ and alloantigen‐activated peripheral blood mononuclear cells (PBMC) from humans and of mitogen‐activated PBMC from cats, cows, sheep, and horses were equivalent. In addition, both molecules were directly mitogenic for human PBMC and induced the production of interferon‐&ggr;. Human PBMC treated with IL‐2 generated enhanced levels of cytotoxic cells against both natural killer (NK)‐sensitive and NK‐resistant targets. In all of these systems and assays, recombinant IL‐2125had the same range of biological activity and potency as homogeneous native IL‐2.

ISSN:0732-6580    

出版商:OVID    

年代:1985

数据来源: OVID