Cytokines, cellular & molecular therapy最新文献

{"title":"Utility of hepatitis C virus serotypes in predicting response to treatment of chronic hepatitis C. Consensus Interferon Study Group.","authors":"E B Keeffe,&nbsp;G M Dusheiko,&nbsp;S P James,&nbsp;K D Mullen,&nbsp;G T Everson,&nbsp;N R Pimstone,&nbsp;J Donovan,&nbsp;D Albert","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Hepatitis C virus (HCV) genotyping has been shown to predict response to interferon, but is expensive. HCV serotyping is less expensive and simpler, and may be similarly useful. Using data from a large, randomized trial comparing consensus interferon (CIFN) and interferon alfa-2b (IFN alfa-2b) in patients with chronic HCV, we evaluated response rates based on HCV serotypes versus genotypes. Patients included in this analysis received subcutaneous injection of 9 microg CIFN (n = 232) or 3 MU IFN alfa-2b (n = 240) three times weekly for 24 weeks followed by 24 weeks of observation. Serum HCV RNA concentrations were measured regularly during treatment and at the end of both the treatment and post-treatment periods. Response to interferon was similar for HCV antibody types and their corresponding genotypes. The end-of-treatment HCV RNA rate of response (defined as undetectable serum on two consecutive assessments) was 29% for serotype 1 versus 24% for genotype 1 after CIFN; and 14% versus 15%, respectively, after IFN alfa-2b. Independently of treatment, patients infected with serotype or genotype 2 or 3 had a better therapeutic response than those infected with serotype or genotype 1. Similar results were obtained based on HCV antibody typing and genotyping, suggesting the potential of the former for predicting response to interferon.</p>","PeriodicalId":79485,"journal":{"name":"Cytokines, cellular & molecular therapy","volume":"5 4","pages":"207-10"},"PeriodicalIF":0.0,"publicationDate":"1999-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"21693922","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Genotype does not affect pattern of HCV RNA decrease among responders during interferon treatment of chronic hepatitis C. Consensus Interferon Study Group.","authors":"E B Keeffe,&nbsp;G M Dusheiko,&nbsp;M J Tong,&nbsp;F B Hollinger,&nbsp;E J Heathcote,&nbsp;J McHutchison,&nbsp;D Albert","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>We assessed differences in the pattern of HCV RNA decrease for HCV genotypes 1, 2, and 3 during interferon treatment to determine if the lower response rates observed among genotype 1 patients were related to a slower decrease in HCV clearance. Serum HCV RNA values of 472 chronic hepatitis C patients treated with either consensus interferon (CIFN) or interferon alfa-2b (IFN alfa-2b) were evaluated. Neither virological sustained responders nor relapsers differed in the pattern of serum HCV RNA decrease based on genotype. Virological sustained responders infected with genotype 1 cleared HCV RNA as rapidly as sustained responders who were infected with genotype 2 or 3. Relapsers had a slower rate of serum HCV RNA decrease than did virological sustained responders. Nonresponders differed in the pattern of serum HCV RNA decrease based on genotype: HCV genotype 3 patients had the greatest decrease in serum HCV RNA; genotype 2 patients had an intermediate decrease; and genotype 1 patients had the least serum HCV RNA decrease. HCV genotype 1 patients treated with CIFN had a greater decrease in serum HCV RNA during therapy than did patients treated with IFN alfa-2b. However, there was no difference in the magnitude of serum HCV RNA decrease between the two interferon treatments for patients infected with genotype 2 or 3. In summary, both genotype and ultimate response to treatment are determinants of the pattern and rate of serum HCV RNA change during interferon therapy of chronic hepatitis C.</p>","PeriodicalId":79485,"journal":{"name":"Cytokines, cellular & molecular therapy","volume":"5 4","pages":"211-6"},"PeriodicalIF":0.0,"publicationDate":"1999-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"21693923","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The effects of GM-CSF, steel factor and MIP-1alpha on the expression and activation of Cdc25A phosphatase in Mo7e cells.","authors":"S Reid,&nbsp;H E Broxmeyer","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Active cyclin-dependent kinases (CDKs) are required for progression through the G1 phase of the cell cycle and entry into S phase. Activity of G1 CDKs is controlled by mechanisms including phosphorylation of Thr14 and Tyr15 residues. Removal of inhibitory phosphates on these amino acid residues is required for G1 CDK activation, and is mediated by the Cdc25A phosphatase. Regulation of active Cdc25A phosphatase levels may be important for the proliferation of hematopoietic progenitor cells, effects assessed in the human growth-factor-dependent cell line Mo7e. Constitutive Cdc25A protein levels were enhanced with granulocyte-macrophage colony-stimulating factor (GM-CSF) plus steel factor (SF). Cdc25A is thought to exert its activity in the nucleus, and nuclear protein levels of Cdc25A were also enhanced with GM-CSF and SF. GM-CSF plus SF promote synergistic growth of Mo7e cells. Pretreatment with macrophage inflammatory protein (MIP-1alpha) inhibited GM-CSF- plus SF-induced growth and upregulation of Cdc25A protein levels. Stimulation with GM-CSF and SF also rapidly increased Cdc25A phosphatase activity, an effect suppressed by MIP-1alpha. A concomitant inhibition of increased CDK4 kinase activity correlated with increased phosphotyrosine levels on CDK4 when cells were pretreated with MIP-1alpha prior to GM-CSF and SF. These data suggest that Cdc25A expression and activity are regulated during proliferation of Mo7e cells.</p>","PeriodicalId":79485,"journal":{"name":"Cytokines, cellular & molecular therapy","volume":"5 3","pages":"129-38"},"PeriodicalIF":0.0,"publicationDate":"1999-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"21497163","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Filgrastim (r-metHuG-CSF) and its potential use in the reduction of radiation-induced oropharyngeal mucositis: an interim look at a randomized, double-blind, placebo-controlled trial.","authors":"S B Schneider,&nbsp;R D Nishimura,&nbsp;R P Zimmerman,&nbsp;L Tran,&nbsp;J Shiplacoff,&nbsp;M Tormey,&nbsp;R Contreras,&nbsp;G F Juillard","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>We wished to determine if filgrastim administration to chemotherapy/radiation therapy-naive patients receiving external-beam irradiation for head-and-neck malignancies would reduce the incidence and severity of oral/oropharyngeal mucositis. Patients were randomized to receive subcutaneous injections of either filgrastim or placebo beginning on day 1 of radiation and continuing daily throughout treatment. Study medication was titrated to keep the neutrophil count between 10 x 10(9) and 30 x 10(9)/l. The left and right buccal mucosa, hard palate, and posterior pharyngeal wall were scored weekly, by a blinded evaluator using two different scales, and the most severe score per week was used in data analysis. Fourteen of a planned 54 patients were randomized (8 filgrastim, 6 placebo), and were evaluable for a planned interim analysis. No statistically significant between-group differences were seen in mean worst scores across time using repeated measures analysis of variance (Hickey, p = 0.231; WHO, p= 0.288). At almost all timepoints, however, the worst mean scores were lower in patients treated with filgrastim compared with those in patients treated with placebo, and the number of severe (i.e., grade 3) mucositis scores was significantly lower in the filgrastim-treated group. Filgrastim may decrease the severity of radiation-induced oral/oropharyngeal mucositis.</p>","PeriodicalId":79485,"journal":{"name":"Cytokines, cellular & molecular therapy","volume":"5 3","pages":"175-80"},"PeriodicalIF":0.0,"publicationDate":"1999-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"21497169","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The incidence of chromosome 9p21 abnormalities and deletions of tumor suppressor genes p15(INK4b)/p16(INK4a)/p14(ARF) in patients with acute lymphoblastic leukemia.","authors":"S Faderl,&nbsp;Z Estrov,&nbsp;H M Kantarjian,&nbsp;D Thomas,&nbsp;J Cortes,&nbsp;T Manshouri,&nbsp;C C Chan,&nbsp;K J Hays,&nbsp;S Pierce,&nbsp;M Albitar","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Cytogenetic changes are of pivotal prognostic significance in patients with de novo acute lymphoblastic leukemia (ALL). However, in some cases leukemic blasts can harbor gene lesions on a submicroscopic level without evidence of a corresponding abnormality by conventional cytogenetic studies. This can result in failure to recognize chromosomal abnormalities and inappropriate evaluation with respect to therapy assignments. To study the discrepancy in the detection of deletions of the short arm of chromosome 9 and deletions of tumor suppressor genes p15/p16/p14 on chromosome 9p21, we analyzed bone marrow samples from 92 patients with ALL both by cytogenetic analysis and by Southern blot. In 41 patients (45%), we found deletions of p15/p16/p14, which were homozygous in 27 and hemizygous in 14. Cytogenetic analysis demonstrated abnormalities of the short arm of chromosome 9 in the form of 9p- or del(9p21-22) in only 5 of the 41 patients (12%). Only 2 of 51 patients without gene deletions as detected by Southern blot revealed a 9p- abnormality, which was found only in a subpopulation of the cells. We demonstrate that deletions of the p15/p16/p14 genes on chromosome 9p21 are more frequent than indicated by cytogenetic analysis. Molecular techniques in addition to cytogenetic studies are necessary to detect otherwise-unrecognized genetic lesions of the short arm of chromosome 9.</p>","PeriodicalId":79485,"journal":{"name":"Cytokines, cellular & molecular therapy","volume":"5 3","pages":"159-63"},"PeriodicalIF":0.0,"publicationDate":"1999-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"21497167","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"TNF-alpha secretion and apoptosis of lymphocytes mediated by gene transfer.","authors":"O Ebert,&nbsp;G Röpke,&nbsp;A Märten,&nbsp;P Lefterova,&nbsp;B Micka,&nbsp;P Buttgereit,&nbsp;S Niemitz,&nbsp;B Trojaneck,&nbsp;G Schmidt-Wolf,&nbsp;D Huhn,&nbsp;B Wittig,&nbsp;I G Schmidt-Wolf","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Efficient gene transfer of lymphocytes is extremely difficult. Apoptosis may play a role in this gene transfer resistance of lymphocytes. Here we show that transfection of lymphocytes via non-viral vectors leads to induction of apoptosis in a significant proportion of cells. Since apoptosis may be mediated via tumor necrosis factor d (TNF-alpha) and the TNF-alpha receptor pathway, we studied the amount of TNF-alpha secreted by lymphocytes transfected without gene insert. TNF-alpha secretion was dependent on the gene transfer method used. High amounts were detected using receptor-mediated gene transfer and lipofection. In contrast, only low amounts of TNF-alpha were detected after electroporation and retroviral gene transfer. In receptor-mediated gene transfer, TNF-alpha secretion was due to the use of anti-CD3 antibody. Transfection of lymphocytes led to selective decrease in CD120b/TNF-alpha receptor II (TNFR-2)-positive cells. Induction of apoptosis and necrosis mediated by TNF-alpha via TNFR-2 (p80) was partially blocked using a neutralizing anti-TNF-alpha antibody. Blockage of apoptosis and necrosis could be further increased by adding anti-Fas-ligand (FasL) antibody, suggesting that induction of apoptosis via FasL and Fas receptor (Apo-1/CD95) may also play a role. This blockage led to a significant increase in the proliferation rate of lymphocytes transfected with cytokine genes. In conclusion, various gene transfer techniques led to TNF-alpha secretion, apoptosis and necrosis of lymphocytes. Apoptosis and necrosis could be partially blocked using a neutralizing anti-TNF-alpha antibody.</p>","PeriodicalId":79485,"journal":{"name":"Cytokines, cellular & molecular therapy","volume":"5 3","pages":"165-73"},"PeriodicalIF":0.0,"publicationDate":"1999-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"21497168","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Allogeneic cell therapy in murine B-cell leukemia (BCL1): 2. The role of non-activated and rIL-2-activated CD4+ and CD8+ T cells in immunotherapy for leukemia.","authors":"L Weiss,&nbsp;S Reich,&nbsp;S Slavin","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Graft-versus-leukemia (GVL) effects play a key role in the elimination of residual leukemia cells in the course of allogeneic bone marrow transplantation (alloBMT). GVL effects can also be induced by donor lymphocyte infusion following alloBMT. We have investigated the role of CD4+ and CD8+ T cells in the development of GVL in mice with B-cell leukemia/lymphoma (BCL1) following allogeneic cell therapy. Sublethally irradiated (C57BL/6 x BALB/c)F1 mice were intravenously inoculated with 10(5) BCL1 cells and given untreated or recombinant human Interleukin-2 (rIL-2)-activated C57BL/6 spleen cells. Effective elimination of clonogenic BCL1 cells was confirmed by adoptive transfer of spleen cells obtained from treated mice into secondary BALB/c recipients. GVL effects were maintained after inactivation of CD4+ cells with monoclonal anti-CD4 antibodies in the inoculum, while inactivation of CD8+ cells with monoclonal anti-CD8 antibodies resulted in complete loss of GVL effects induced both by resting and rIL-2-activated allogeneic spleen lymphocytes. These results indicate that Thy-1 cells play the major role in the induction of GVL effects, mediated by C57BL/6 effector T cells in this model. Since the number of natural killer (NK) cells also increased during in vitro culture with rIL-2, their contribution, especially that of CD8+ NK cells, in GVL effects mediated by rIL-2-activated CD8+ cells cannot be ruled out.</p>","PeriodicalId":79485,"journal":{"name":"Cytokines, cellular & molecular therapy","volume":"5 3","pages":"153-8"},"PeriodicalIF":0.0,"publicationDate":"1999-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"21497166","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Intradermal injection of granulocyte-macrophage colony-stimulating factor (GM-CSF) in patients with metastatic melanoma recruits dendritic cells.","authors":"M L Nasi,&nbsp;P Lieberman,&nbsp;K J Busam,&nbsp;V Prieto,&nbsp;K S Panageas,&nbsp;J J Lewis,&nbsp;A N Houghton,&nbsp;P B Chapman","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Dendritic cells (DCs) are the main antigen-presenting cells in the skin. We hypothesized that intradermal (i.d.) injection of granulocyte-macrophage colony-stimulating factor (GM-CSF) would recruit DCs into melanoma skin metastases and enhance autologous melanoma antigen presentation to host T cells. Sixteen patients with cutaneous or subcutaneous melanoma metastases were treated with GM-CSF injected i.d. into a single dermal metastasis and into a normal skin site for 10 consecutive days at one of four dose levels (10, 20, 40, or 80 microg/injection). Pretreatment and post-treatment skin and tumor biopsies were stained for a panel of T-cell, B-cell, macrophage, and DC immunohistochemical markers. Positive cells were quantitated in a blinded fashion. There was a significant increase in the number of DCs (HLA-DR+, S100+, factor XIIIa+) and CD45R0+ T cells in the skin and in the tumors Injected with GM-CSF at all dose levels. Uninjected control tumors showed no increase in HLA-DR+ cells or T-cell infiltrate, but did show an Increase in S100+ and factor XIIIa+ cells, suggesting a non-DC population. ID GM-CSF administered in this manner recruited DCs into melanoma tumors and normal skin. Although no antitumor effects were seen, this represents a potential method of preparing skin sites for vaccine delivery.</p>","PeriodicalId":79485,"journal":{"name":"Cytokines, cellular & molecular therapy","volume":"5 3","pages":"139-44"},"PeriodicalIF":0.0,"publicationDate":"1999-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"21497164","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Allogeneic cell therapy in murine B-cell leukemia (BCL1): 1. Alloimmune-mediated graft-versus-leukemia (GVL) effects induced by unmodified and in vitro rIL-2-activated bone marrow and lymphocytes from different lymphoid compartments.","authors":"L Weiss,&nbsp;S Reich,&nbsp;S Slavin","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>We have investigated the efficacy of graft-versus-leukemia (GVL) effects induced by cells obtained from different syngeneic and allogeneic lymphoid compartments, by comparing the response to cell therapy with syngeneic (BALB/c x C57BL/6)F1 (H-2d/b) (F1) or allogeneic C57BL/6 (H-2b) (B6) lymphocytes in F1 recipients inoculated with B-cell leukemia (BCL1) of BALB/c (H-2d) origin. Eradication of BCL1 was confirmed in vivo by adoptive transfer of 10(5) spleen cells obtained from treated mice into syngeneic BALB/c recipients. Immunotherapy induced by allogeneic but not syngeneic spleen and lymph node lymphocytes was therapeutically more effective than thymocytes and bone marrow cells (BMC). Alloreactive cells could be further activated in vivo with recombinant human interleukin-2 (rIL-2). The GVL effect of allogeneic lymphocytes was cell-dose-dependent; a heavy leukemia load was more efficiently eradicated after three doses than after a single dose of allogeneic spleen cells (100% versus 23% disease-free survival rate of secondary adoptive recipients respectively). The GVL effect induced by allogeneic spleen cells was preserved after ex vivo exposure of cells to 250 cGy, but not 500 cGy or more. Interestingly, GVL was preserved following administration of ex vivo irradiated (500 cGy) spleen cells when rIL-2 was administered in vivo (p < 0.05). Syngeneic effector cells did not induce GVL, regardless of in vitro and in vivo activation with rIL-2. Our data suggest that allogeneic but not syngeneic (in analogy to autologous) cell therapy may be an effective tool to control residual leukemia following high-dose chemo-radiotherapy. The feasibility of augmenting GVL by successive doses of activated allogeneic donor lymphocytes, partly inactivated in vitro by low-dose ionizing irradiation to prevent severe graft-versus-host disease (GVHD), may lead to safer therapeutic approaches that can be used to reduce the incidence of relapse while avoiding the risk of uncontrolled GVHD.</p>","PeriodicalId":79485,"journal":{"name":"Cytokines, cellular & molecular therapy","volume":"5 3","pages":"145-52"},"PeriodicalIF":0.0,"publicationDate":"1999-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"21497165","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Interleukin-3 in hematology and oncology: current state of knowledge and future directions.","authors":"M H Mangi,&nbsp;A C Newland","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Interleukin (IL)-3 is a multipotent hematopoietic growth factor produced by activated T cells, monocytes/macrophages and stroma cells. The human IL-3 gene is located on chromosome 5 near segment 5q31. The high-affinity receptor for human IL-3 is composed of alpha and beta subunits. IL-3 shares a common beta subunit with granulocyte-macrophage colony-stimulating factor (GM-CSF) and IL-5; this subunit has been mapped to chromosome 22q13.1. The biological effects of IL-3 have been studied in human and murine hematopoietic cell lines and normal human marrow cells. Addition of IL-3 to the culture medium induces proliferation, maturation and probably self-renewal of pluripotent hematopoietic stem cells and cells of myeloid, erythroid and megakaryocytic lineages. Human IL-3 was cloned in 1986, and since then various clinical trials have assessed the in vivo potential of recombinant human (rhIL-3). Initial results of phase I/II studies of IL-3 at a dose of 5-10 microg/kg subcutaneously daily for 5-10 days in patients with relapsed lymphomas, small-cell lung cancer, breast cancer and ovarian cancer showed that post-chemotherapy application of IL-3 reduces chemotherapy delays and induces faster regeneration of granulocytes and platelets. However, these results were not confirmed in phase III studies. The role of IL-3 alone in the treatment of myelodysplastic syndromes (MDS), aplastic anemia (AA) and other bone marrow failure disorders have also been disappointing. However, preliminary studies of IL-3 in combination with chemotherapeutic agents and immunosuppression have demonstrated encouraging results in patients with MDS and AA respectively. The therapeutic potential of IL-3 in peripheral blood stem cell (PBSC) harvesting and priming of stem cells before harvest is beginning to be identified. Initial results of IL-3 combination with GM-CSF or later-acting growth factors such as granulocyte colony-stimulating factor (G-CSF) have yielded larger amounts of PBSC during harvesting. In recent years, the availability of synthetic IL-3 receptor (IL-3R) agonists and similar chimeric molecules with greater in vitro biological activity and fewer inflammatory side-effects has extended our options to employ and compare these molecules and rhIL-3 for the prevention of chemotherapy-induced myelosuppression. The role of IL-3 and IL-3R agonists in ex vivo expansion of stem cells, dendritic cell development and gene transfer requires further evaluation. It appears that future application of IL-3 in combination with other cytokines is an attractive way forward in the prevention of treatment-related mortality and morbidity in oncology patients. It also shows prospects for the development of new therapeutic strategies for dose escalation and immune modulation for cancer patients with relapsed and resistant disease.</p>","PeriodicalId":79485,"journal":{"name":"Cytokines, cellular & molecular therapy","volume":"5 2","pages":"87-95"},"PeriodicalIF":0.0,"publicationDate":"1999-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"21377651","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}