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:We investigated the effects of retinoic acid (RA) on natural killer (NK) cell activity and on the susceptibility of various tumor target cells to NK cell lysis. These studies were undertaken to assess the overall effects of RA treatment on the natural killing of tumor cells in humans. We also evaluated how RA affects the generation of NK‐like activity in mixed leucocyte culture, to determine whether or not this compound can influence the regulation of natural cytotoxicity during the induction phase of NK cell development. Our results indicate that pharmacological levels of RA have little, if any, influence on the development, cytotoxic potential, or activity of NK cells in humans. In contrast, RA can significantly reduce the sensitivity of some tumor target cells to natural killing. This effect appears to be directly related to the differentiation‐promoting properties of RA, since reduced NK susceptibility was observed with target cells that were “differentiated” by RA treatment, but not with cells that were either unaffected by RA or were only growth inhibited without concomitant differentiation. These findings indicate that the immunomodulating properties of RA do not extend to human NK cell activity. However, a possible decreased susceptibility of tumor cells to natural killing should be a consideration when planning therapeutic applications of RA in certain cancers.

ISSN:0732-6580    

出版商:OVID    

年代:1985

数据来源: OVID

摘要:

Summary:Peripheral blood lymphocytes (PBL) primed in vitro with irradiated allogeneic PBL can suppress alloactivated proliferation of fresh autologous PBL in a primary mixed lymphocyte culture (MLC). Proliferation of fresh PBL was measured by tritiated thymidine uptake after 6 days of coculture with irradiated fresh allogeneic stimulator PBL; irradiated autologous primed PBL were added to assess suppression. These primed cells had been cultured for 6 to 10 days prior to their irradiation and addition to a primary MLC. Suppression in this assay by PBL primed for 6 days was inversely correlated with radiation dose. The addition of highly purified recombinant interferon‐&agr; (IFN) during the 6‐day priming of these lymphocytes did not alter their suppressive ability, nor did it alter the radiation sensitivity of their suppression. In contrast, PBL primed for 10 days were highly suppressive even if irradiated before their addition to the assay. However, when PBL were primed for 10 days in the presence of IFN, their ability to suppress was again radiation sensitive. These data suggest that between days 6 and 10 of primary MLC, IFN inhibits either proliferation or differentiation of a lymphocyte population involved in the generation of radioresistant suppressive activity.

ISSN:0732-6580    

出版商:OVID    

年代:1985

数据来源: OVID

摘要:

Summary:Several protocols employing a new immunoadjuvant, maltose tetrapalmitate (MTP), were tried in an effort to obtain immunization against a weakly immunogenic transplantable mammary adenocarcinoma, 13762, in syngeneic Fischer rats. Effectiveness of immunization was measured by rejection of tumor or reduction in tumor growth, by alteration in survival time after tumor challenge, and by proliferation in vitro of spleen cells of animals tumor‐sensitized by killed tumor cells and tumor extracts. No success in the induction of tumor rejection was achieved by employing killed tumor cells or 3MKC1 tumor extracts used in either the presence or absence of MTP. Only a low dose of viable tumor cells elicited tumor rejection immunity when combined with MTP treatment given three times weekly. Spleen cell proliferation of tumor‐sensitized animals was obtained in the case of live cells and 3MKC1 extract immunization, and was specific for the type of antigen (killed cells or soluble) preparation employed.

ISSN:0732-6580    

出版商:OVID    

年代:1985

数据来源: OVID

摘要:

Summary:Recombinant DNA‐produced interferon‐&ggr; (rIFN‐&ggr;) was administered intravenously to patients with solid tumors in a Phase I study. The rIFN&ggr; was prepared fromEscherichia coliand purified to >95% with a specific activity of ≥30 × 106units/mg protein. Twenty patients received intravenous bolus injections once weekly for 4 consecutive weeks. They were assigned to one of six dose groups ranging from 1 to 81 × 106units/m2body surface area; intrapatient dose escalation was not allowed. Patients were monitored intensively for toxicity, but no dose‐limiting toxicity was demonstrated. Fever was the predominant side effect, occurring in all patients treated, and usually reached 38‐40°C. Short‐term somnolence and fatigue were also observed, but no chronic fatigue was seen. Decreases in white blood cell and platelet counts, generally within the normal range, were observed; however, the counts rose again after intervals of 2‐5 days. There was no firm evidence of a relationship between adverse effects and dose. No life‐threatening side effects were noted and no antibodies developed to either rIFN&ggr; orE. coliproteins. the pharmacokinetics of rIFN&ggr; did not appear to alter from week 1 to week 4. Calculated half‐lives were from 0.8 to 3.5 h. Doses >9 × 106units/m2gave measurable serum levels for at least 12 h. A partial response of 8 weeks' duration was observed in a patient with hepatoma.

ISSN:0732-6580    

出版商:OVID    

年代:1985

数据来源: OVID

摘要:

Summary:Balb/c mice were immunized with membrane preparations of primary and metastatic breast carcinomas or with live breast cancer cell lines. Sixty‐two fusions were performed between immune splenocytes and SP2/0 mouse myeloma cells, and 107 hybridomas were cloned that produced antibody reactive with breast cancer membrane extract, cell lines, and frozen sections, but not with normal tissue membrane extracts or a human fibroblast line. Ninety‐four monoclonal antibodies were purified and tested for binding to 16 normal tissue frozen sections and five blood cell types. Thirty‐five of the 94 antibodies were also tested on breast cancer sections from 21 patients, 14 breast cancer cell lines, and 11 non‐breast tumor sections. Two of 94 antibodies showed no reactivity to any of the 21 normal tissues or 11 nonbreast neoplasms studied. These two antibodies, 451B7 and 452F2, bound 60% of the breast cancer cell lines and 25% of the breast cancer tissue sections. Eight additional antibodies bound three or fewer of 21 normal tissues. These antibodies bound 25‐85% of breast cancer sections, 0‐75% of breast cancer cell lines, and many of the nonbreast cancers. A comparison of normal tissues and nonbreast tumors bound by the breast cancer‐reactive antibodies indicated that most of the cross‐reacting normal tissue structures were epithelial in origin, and that the most cross‐reactive nonbreast cancers were those of secondary sex organs (uterus, prostate, ovary).

ISSN:0732-6580    

出版商:OVID    

年代:1985

数据来源: OVID

摘要:

Summary:We studied the effect of cloned human interferons‐&agr; and ‐&bgr; (IFN‐&agr; and IFN‐&bgr;) upon human peripheral blood lymphocytes stimulated in primary mixed lymphocyte cultures (MLC). We herein demonstrate that three of these IFN preparations (IFN‐&agr;76, ‐&agr;54, ‐&bgr;ser), as well as naturally produced IFN‐&bgr;, can each affect MLC in opposing ways. When stimulator cells are limited, IFN‐&agr; and ‐&bgr; are inhibitory. At higher stimulating cell concentrations, IFN augments the MLC response. This potentiation of the proliferative response is IFN dose‐dependent and is not due to a shift in the kinetics of the proliferative response. When T cell clones were tested in the proliferative assay, IFN‐&agr;76was shown to have a direct antiproliferative effect. Both the potentiation and inhibition of primary bulk MLC responses could result from the direct antiproliferative effect of exogenous IFN. The potentiation of some proliferative responses by IFN in bulk culture may reflect a preferential inhibition of immunoregulatory (suppressor) cells. Moreover, these dichotomous effects of IFN on primary alloactivated cultures suggest that caution should be used when extrapolating from these in vitro results to potential in vivo effects.

ISSN:0732-6580    

出版商:OVID    

年代:1985

数据来源: OVID

摘要:

Summary:Muramyl dipeptide and muramyl tripeptide in free form or encapsulated within multilamellar liposomes were injected intravenously into (C57BL/6 × C3H)F1 mice and strain 2 guinea pigs to evaluate their potential acute, subacute, or chronic toxicity. Animals received either single or multiple (× 3, × 4, × 6, × 8) injections. A definite species variation was established with regard to the toxic nature of muramyl peptides. Mice failed to exhibit any changes of a clinical, biochemical, functional, or morphological nature in response to repeated intravenous administrations of high doses of muramyl peptide (free or in liposomes). In contrast, strain 2 guinea pigs were very sensitive to muramyl peptide, regardless of the dose or number of injections, or whether it was given in liposomes or as micelles (free form). Most guinea pigs exhibited vascular pathology reminiscent of the Schwartzman phenomenon. Further toxicity studies of muramyl peptides administered at relevant biological doses are recommended, as well as studies aimed at elucidating the reasons for the species variations.

ISSN:0732-6580    

出版商:OVID    

年代:1985

数据来源: OVID

摘要:

Summary:Eight previously treated and four untreated patients with B cell chronic lymphocytic leukemia (CLL) received 20 × 106U/m2recombinant leukocyte interferon clone A (rIFN‐&agr;A) intramuscularly three times a week for 8 weeks. None of the eight patients who had received prior chemotherapy exhibited objective evidence of tumor regression. Two of the four previously untreated patients responded with transient (90%) decreases in absolute lymphocyte counts lasting for 2 and 7 months. Toxicity was moderate, with all patients experiencing a flu‐like syndrome requiring a 50% dose reduction. Half of the patients exhibited anorexia, weight loss, and a drop in performance status. The two responders had normal serum immunoglobulin levels prior to treatment, whereas 80% of non‐responders had depressed levels. Treatment with rIFN‐&agr;A was associated with a depression of nonspecific and specific humoral immunity in assays employing cryopreserved autologous pretherapy CLL cells. No consistent effects were demonstrable in cytolytic assays with purified peripheral blood T cells as effector cells, including one that utilized autologous CLL target cells. rIFN‐&agr;A has limited antitumor activity in B cell CLL which is restricted to untreated patients with an early stage of disease. With the assays employed it was not possible to demonstrate that rIFN‐&agr;A could augment autologous antitumor immunity.

ISSN:0732-6580    

出版商:OVID    

年代:1985

数据来源: OVID