Journal of immunotherapy : official journal of the Society for Biological Therapy最新文献

{"title":"Can't Get Any Help? New Approaches for Adoptive Immunotherapy of Cancer.","authors":"C. June","doi":"10.1097/00002371-200109000-00001","DOIUrl":"https://doi.org/10.1097/00002371-200109000-00001","url":null,"abstract":"","PeriodicalId":77209,"journal":{"name":"Journal of immunotherapy : official journal of the Society for Biological Therapy","volume":"39 1","pages":"389-391"},"PeriodicalIF":0.0,"publicationDate":"2001-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"78616947","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":"Hierarchy, Tolerance, and Dominance in the Antitumor T-Cell Response.","authors":"Nicholas P. Restifo","doi":"","DOIUrl":"","url":null,"abstract":"","PeriodicalId":77209,"journal":{"name":"Journal of immunotherapy : official journal of the Society for Biological Therapy","volume":"24 3","pages":"193-194"},"PeriodicalIF":0.0,"publicationDate":"2001-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144175679","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":"Hierarchy, Tolerance, and Dominance in the Antitumor T-Cell Response.","authors":"N. Restifo","doi":"10.1097/00002371-200105000-00001","DOIUrl":"https://doi.org/10.1097/00002371-200105000-00001","url":null,"abstract":"T-cell responses to any given epitope can be inhibited or “dominated” by simultaneous exposure to antigens on the same or different molecules (1, 2), but the molecular events underlying the phenomenon of immunodominance are poorly understood. The reasons why one epitope is immunodominant are complex, but one quality that immunodominant epitopes from viruses share is that they tend to be among the peptide fragments that are best able to form high-affinity, stable complexes with restricting major histocompatibility class (MHC) molecules. A report in this issue addresses the question of why the best-binding, most immunodominant epitopes of the type generally discovered by virologists may not be the ones found by tumor immunologists (3). \u0000 \u0000With the identification of tumor-associated antigens recognized by T cells in the early 1990s, there were vigorous debates about whether the epitopes that had been identified were indeed correct. In the case of melanoma, the affinities of the epitopes from melanocyte differentiation antigens seemed to be significantly lower than expected. In some cases, such as what appears to be the immunodominant epitope from human MART-1 restricted by HLA-A*0201 (4), the affinity of the peptide epitope was logs lower than the affinities measured for viral epitopes with the same restriction element. First viewed by some as an aberration, it now appears that the antigenic epitopes recognized by tumor-reactive T cells can often bind with relatively poor avidity to their restricting MHC molecules. \u0000 \u0000Predicting immunodominant peptides that can be targets for recognition by T cells, also known as allele-specific epitope forecasting, can be done in a variety of ways, but one of the best predictors is the use of computer programs that predict the ability of peptides to form stable complexes with T cells. One of these computer programs is designed for a wide variety of MHC alleles and is available on a public website at http://bimas.cit.nih.gov/molbio/hla_bind/ \u0000 \u0000Viewed from the world of viral immunology, the ability of some tumor-derived peptides to form stable complexes with their restricting HLA molecules is poor. For example, an epitope derived from melanoma antigen recognized by T-cell 1 (MART-1) starting at position 27 and having the amino acid sequence AAGIGILTV is ranked ninth of all possible nonamers from this relatively small protein. Perhaps more striking, its predicted half-time of disassociation from HLA-A*0201 is 580-fold lower than the best possible nonamer binder from MART-1. In another example, gp100, a particularly useful peptide with a starting position of 209 (5), is ranked 46th of all possible nonamers and has a predicted half-time of disassociation that is approximately 390-fold lower than the best binder in the molecule. A similarly poor binder for self-gp100 was found in the mouse (6). \u0000 \u0000One key difference between many tumor antigens and those from the world of virology is that these antigens are present on no","PeriodicalId":77209,"journal":{"name":"Journal of immunotherapy : official journal of the Society for Biological Therapy","volume":"69 1","pages":"193-194"},"PeriodicalIF":0.0,"publicationDate":"2001-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"81411526","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":"A Prospective, Randomized, Double-Blind, Placebo-Controlled Trial Evaluating the Effect of Nystatin on the Development of Oral Irritation in Patients Receiving High-Dose Intravenous Interleukin-2.","authors":"G. A. Ohnmacht, G. Phan, S. Mavroukakis, S. Steinberg, Y. Shea, F. Witebsky, Lori S. McIntyre, R. Goodwin, P. Muehlbauer, K. Morton, Linda J. Rogers-Freezer, C. Seipp, S. Rosenberg, F. Marincola","doi":"10.1097/00002371-200103000-00014","DOIUrl":"https://doi.org/10.1097/00002371-200103000-00014","url":null,"abstract":"SUMMARY: Interleukin-2 (IL-2) has been used to treat patients with metastatic melanoma and renal cell cancer for nearly two decades, and much progress has been made in ameliorating its adverse effects. One bothersome adverse effect, oral pain or oral irritation, is usually treated with an oral antifungal antibiotic, nystatin. The authors performed a prospective, randomized, double-blind, placebo-controlled trial involving 64 patients to evaluate the effect of prophylactic administration of nystatin or placebo on the development of oral irritation in patients receiving high-dose intravenous IL-2. No difference was found between patients randomized to receive nystatin or placebo in their rates of development of oral irritation, the severity of IL-2 adverse effects, the duration of their treatment, the rate of development of positive studies for oral yeast, or their pattern of experiencing other adverse effects. Thus, patients who receive high-dose intravenous IL-2 should not be treated prophylactically with nystatin to prevent oral irritation, and clinicians should seek evidence of the presence of oral thrush before using antifungal agents to treat oral pain in these patients.","PeriodicalId":77209,"journal":{"name":"Journal of immunotherapy : official journal of the Society for Biological Therapy","volume":"33 1","pages":"188-192"},"PeriodicalIF":0.0,"publicationDate":"2001-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"76670326","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":"Tumor-Dendritic Cell Fusion Technology and Immunotherapy Strategies.","authors":"S. Shu, P. Cohen","doi":"10.1097/00002371-200103000-00001","DOIUrl":"https://doi.org/10.1097/00002371-200103000-00001","url":null,"abstract":"","PeriodicalId":77209,"journal":{"name":"Journal of immunotherapy : official journal of the Society for Biological Therapy","volume":"167 1","pages":"99-100"},"PeriodicalIF":0.0,"publicationDate":"2001-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"74252943","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":"Herpes simplex-1 virus thymidine kinase gene is unable to completely eliminate live, nonimmunogenic tumor cell vaccines.","authors":"P T Golumbek,&nbsp;F M Hamzeh,&nbsp;E M Jaffee,&nbsp;H Levitsky,&nbsp;P S Lietman,&nbsp;D M Pardoll","doi":"10.1097/00002371-199211000-00002","DOIUrl":"https://doi.org/10.1097/00002371-199211000-00002","url":null,"abstract":"<p><p>Recent experiments with genetically engineered tumors have generated renewed interest in active cellular immunotherapy as a cancer treatment modality. In order to consider the use of live tumor cells for immunotherapy in human cancer patients, it will be important to ensure that these cells do not themselves produce morbidity in the event the immune system fails to eliminate them. Toward this end, we have examined a strategy for eliminating genetically manipulated nonimmunogenic tumors in vivo. When B16F10 melanoma cells were transfected with the Herpes simplex virus 1 thymidine kinase (HSV-TK) gene, cells were rendered susceptible to killing by the nucleoside analogs acyclovir (ACV) and ganciclovir (GCV). B16-HSV-TK+ tumors established in C57BL6 mice were successfully \"suicided\" in vivo when GCV was administered by continuous infusion. However, late recurrences were observed even after 1 month of continuous GCV treatment. In vivo growth kinetics suggested that the recurrences resulted from a tiny number (< 20) of cells that had survived the GCV treatment. Interestingly, recurrent tumors were as sensitive to GCV as the parental B16-HSV-TK+ line. While these results demonstrate potential feasibility of the suicide gene strategy for active immunotherapy with live tumor cells, they also illustrate that approaches dependent on the intracellular generation of cell cycle-dependent toxins may fail to eliminate small numbers of cells that temporarily exit cell cycle or that are pharmacologically sequestered.</p>","PeriodicalId":77209,"journal":{"name":"Journal of immunotherapy : official journal of the Society for Biological Therapy","volume":"12 4","pages":"224-30"},"PeriodicalIF":0.0,"publicationDate":"1992-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1097/00002371-199211000-00002","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"12508884","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":"A pilot study of the combination of interleukin-2-based immunotherapy and radiation therapy.","authors":"J R Lange,&nbsp;A A Raubitschek,&nbsp;B A Pockaj,&nbsp;W F Spencer,&nbsp;M T Lotze,&nbsp;S L Topalian,&nbsp;J C Yang,&nbsp;S A Rosenberg","doi":"10.1097/00002371-199211000-00007","DOIUrl":"https://doi.org/10.1097/00002371-199211000-00007","url":null,"abstract":"<p><p>A clinical trial was undertaken to evaluate the feasibility of combining radiation therapy and immunotherapy. Twenty-eight patients with metastatic cancer were treated with rapid fractionation radiation up to 2,000 cGy, followed within 24 h by a course of interleukin 2 (IL-2) at 720,000 IU/kg or tumor-infiltrating lymphocytes (TILs) and IL-2 at 720,000 IU/kg. All patients tolerated treatment without any apparent increase in toxicity referable to the irradiation. Four patients had significant shrinkage of tumor at the irradiated site. Only two patients showed significant tumor shrinkage both inside and outside of the irradiated field. While rapid fractionation radiation can be safely administered in combination with immunotherapy, we observed no apparent synergy in antitumor effect in this small number of patients.</p>","PeriodicalId":77209,"journal":{"name":"Journal of immunotherapy : official journal of the Society for Biological Therapy","volume":"12 4","pages":"265-71"},"PeriodicalIF":0.0,"publicationDate":"1992-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1097/00002371-199211000-00007","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"12646441","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-6 increases carcinoembryonic antigen and histocompatibility leukocyte antigen expression on the surface of human colorectal carcinoma cells.","authors":"C D Ullmann,&nbsp;J Schlom,&nbsp;J W Greiner","doi":"10.1097/00002371-199211000-00003","DOIUrl":"https://doi.org/10.1097/00002371-199211000-00003","url":null,"abstract":"<p><p>Human colorectal carcinoma cells that were treated in vitro with interleukin-6 (IL-6) expressed increased levels of carcinoembryonic antigen (CEA) and normal histocompatibility leukocyte antigen (HLA) class I on their cell surface. The IL-6 mediated increase of CEA expression on the surface of a moderately differentiated colon carcinoma cell line (WiDr) was time- and dose-dependent. A 5-day treatment of the WiDr cells with 100 U IL-6/ml increased the percentage of cells that expressed CEA from 29 to > 80% and enhanced the level of HLA class I expression. The increase in CEA expression as a result of IL-6 treatment was also observed using SDS-PAGE/Western blot analyses, and subsequent Northern blot analyses revealed concomitant increases in CEA-related mRNA transcripts. A comparison of the increases in CEA expression after IL-6, interferon-beta, and interferon-gamma on a nanomolar basis revealed that IL-6 was more potent than either of the interferons. Of 11 different human colorectal tumor cell lines that were treated with IL-6, CEA and/or HLA class I expression were increased in five. Thus, IL-6 can act directly on human colon carcinoma cells and selectively increase the expression of CEA and HLA class I antigens, which may provide some insight into the mechanisms involved in the ability of IL-6 to suppress in vivo tumor growth.</p>","PeriodicalId":77209,"journal":{"name":"Journal of immunotherapy : official journal of the Society for Biological Therapy","volume":"12 4","pages":"231-41"},"PeriodicalIF":0.0,"publicationDate":"1992-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1097/00002371-199211000-00003","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"12646438","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":"Repetitive weekly cycles of 4-day continuous infusion of recombinant interleukin-2: a phase I study.","authors":"K C Punt,&nbsp;R L Jansen,&nbsp;P H De Mulder,&nbsp;D Batchelor,&nbsp;A Galazka,&nbsp;R L Bolhuis,&nbsp;G Stoter","doi":"10.1097/00002371-199211000-00009","DOIUrl":"https://doi.org/10.1097/00002371-199211000-00009","url":null,"abstract":"A phase I trial was performed with a new interleukin-2 (IL-2) given as a continuous intravenous infusion in patients with solid tumors. The objectives of the study were to examine the feasibility of administering IL-2 in 4-day cycles for 4 consecutive weeks, and to investigate the response pattern of peripheral blood lymphocytes. Tumor necrosis factor (TNF) and IL-2 serum concentrations were also measured. Prior to this study, IL-2 had been tested at increasing dosages during one 4-day cycle, and it appeared that a dose of 1300 mcg/m2/day was tolerated. However, when this treatment schedule was maintained for 4 consecutive weeks, the maximum tolerated dose was 430 mcg/m2/day. In this schedule, a dose-dependent progressive increase in rebound lymphocyte count occurred after each weekly cycle, resulting in a 5-70-fold increase after the 4th cycle. Serum TNF peak concentrations also showed a tendency to increase during each subsequent cycle, while serum IL-2 peak concentrations showed a paradoxical decrease. Clinical toxicity comprised several events, which, possibly, could be ascribed to autoimmune phenomena. Myocardial infarction as a late toxicity of IL-2 is suggested. One complete response (renal carcinoma) and two partial responses (renal and breast carcinoma) were documented, one of these occurring in a patient who previously had shown a transient response on interferon therapy.","PeriodicalId":77209,"journal":{"name":"Journal of immunotherapy : official journal of the Society for Biological Therapy","volume":"12 4","pages":"277-84"},"PeriodicalIF":0.0,"publicationDate":"1992-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1097/00002371-199211000-00009","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"12646443","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":"Improving responses in hepatomas with circadian-patterned hepatic artery infusions of recombinant interleukin-2.","authors":"M M Kemeny,&nbsp;G Alava,&nbsp;J M Oliver","doi":"10.1097/00002371-199211000-00001","DOIUrl":"https://doi.org/10.1097/00002371-199211000-00001","url":null,"abstract":"<p><p>Previous studies on continuous hepatic artery infusions of recombinant interleukin-2 (IL-2) have shown that in a nontumor-bearing animal a continuous infusion given in a circadian \"day cycled\" pattern was much less toxic and could be given with 10 times higher doses of IL-2 than if the constant pattern of infusion was used. In the present study, circadian-patterned continuous hepatic artery infusions of IL-2 were used in hepatoma-bearing rats. Doses of 10 mg/m2/day could be tolerated when IL-2 was given in a \"day cycle\" rhythm. Control animals were given 1 mg/m2/day of constant infusion IL-2, which was the highest hepatic artery infusion dose tolerated at a constant rate without mortality in nontumor-bearing animals. Animals treated with the constant infusions of IL-2 had a 37.5% mortality rate and a 25% objective response rate in measurable tumor size. Animals receiving the \"day cycle\" had no mortality and a 100% objective response rate. The conclusion was that \"day cycled\" circadian-patterned continuous hepatic artery infusions of IL-2 could be given with much lower toxicity and much improved tumor response rates than constant continuous infusions.</p>","PeriodicalId":77209,"journal":{"name":"Journal of immunotherapy : official journal of the Society for Biological Therapy","volume":"12 4","pages":"219-23"},"PeriodicalIF":0.0,"publicationDate":"1992-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1097/00002371-199211000-00001","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"12646437","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}