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

{"title":"Lack of antihypertensive effect of interleukin-2 administration in humans.","authors":"B A Pockaj,&nbsp;S A Rosenberg","doi":"10.1097/00002371-199112000-00010","DOIUrl":"https://doi.org/10.1097/00002371-199112000-00010","url":null,"abstract":"<p><p>A recent study reported that a single bolus dose of interleukin-2 (IL-2) decreased blood pressure to normal in adult hypertensive rats and prevented the development of spontaneous hypertension in young rats. The Surgery Branch of the National Cancer Institute has had extensive experience with the administration of IL-2. A review was performed focusing on the experience of IL-2 administration to cancer patients with established preexisting hypertension. Seventeen evaluable patients were identified. Sixteen of the patients experienced a return of their hypertension with the completion of therapy. One patient was able to stop his antihypertensive medications and remain normotensive for 3 months' follow-up. One normotensive patient developed hypertension after initiating IL-2 therapy. Our data do not demonstrate significant reduction in blood pressure in previously hypertensive patients undergoing high-dose IL-2 therapy.</p>","PeriodicalId":77209,"journal":{"name":"Journal of immunotherapy : official journal of the Society for Biological Therapy","volume":"10 6","pages":"456-9"},"PeriodicalIF":0.0,"publicationDate":"1991-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1097/00002371-199112000-00010","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"12930745","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":"Phase II studies of recombinant human tumor necrosis factor alpha in patients with malignant disease: a summary of the Southwest Oncology Group experience.","authors":"E M Hersh,&nbsp;B S Metch,&nbsp;F M Muggia,&nbsp;T D Brown,&nbsp;R P Whitehead,&nbsp;G T Budd,&nbsp;J J Rinehart,&nbsp;E D Crawford,&nbsp;J D Bonnet,&nbsp;B C Behrens","doi":"10.1097/00002371-199112000-00006","DOIUrl":"https://doi.org/10.1097/00002371-199112000-00006","url":null,"abstract":"<p><p>From June 1988 to November 1990 the Southwest Oncology Group initiated nine protocols for the phase II evaluation of recombinant human tumor necrosis factor alpha (rhuTNF alpha) in cancer patients. Patients with diverse metastatic malignancies including breast, colon, gastric, pancreatic, endometrial, and bladder cancers, as well as multiple myeloma and various sarcomas received 150 micrograms/m2 of rhuTNF alpha daily for 5 days every other week. Of 147 patients entered in the study, 127 were eligible and were evaluated for toxicity and response. Of 124 patients known to have completed treatment, 92 (74%) went off study for progression, 21 (17%) for toxicity, and 12 (10%) for other causes, mainly that of worsening medical condition. Thirteen percent of patients experienced grade 4 or fatal toxicity. The most serious toxicities were pulmonary failure and coagulopathies. The predominant grade 3 toxicities were symptomatic (chills, fever, malaise, headache, myalgia, and nausea or vomiting). Only one partial remission was seen in a patient with metastatic bladder cancer lasting 4 months (rate 0.8%, exact 95% confidence interval 0-4%). At the study dose and schedule, rhuTNF alpha does not appear to have significant antitumor activity. The biological basis for this finding is discussed.</p>","PeriodicalId":77209,"journal":{"name":"Journal of immunotherapy : official journal of the Society for Biological Therapy","volume":"10 6","pages":"426-31"},"PeriodicalIF":0.0,"publicationDate":"1991-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1097/00002371-199112000-00006","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"12930809","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":"Study of tumor-infiltrating lymphocytes for adoptive therapy of renal cell carcinoma (RCC) and metastatic melanoma: sequential proliferation of cytotoxic natural killer and noncytotoxic T cells in RCC.","authors":"K Hayakawa,&nbsp;M A Salmeron,&nbsp;D R Parkinson,&nbsp;A B Markowitz,&nbsp;A C von Eschenbach,&nbsp;S S Legha,&nbsp;C M Balch,&nbsp;M I Ross,&nbsp;L B Augustus,&nbsp;K Itoh","doi":"10.1097/00002371-199110000-00003","DOIUrl":"https://doi.org/10.1097/00002371-199110000-00003","url":null,"abstract":"<p><p>We investigated the immunological properties of interleukin-2 (IL-2)-activated tumor-infiltrating lymphocytes (TIL), which were used for adoptive therapy of renal cell carcinoma (RCC) (seven patients) by focusing on natural killer (NK) cells, and metastatic melanoma (six patients) by focusing on cytotoxic T lymphocytes. TIL from five of seven cases proliferated well in culture with AIM-V serum-free medium and 1000 U/ml rIL-2 in 3-L gas permeable bags, whereas TIL from two RCCs exhibited delayed proliferation. Proliferation of CD3-CD56+ NK cells with major histocompatibility complex-nonrestricted cytotoxicity in RCC-TIL (n = 6, mean = 651-fold, ranging from 39- to 3450-fold) for the first 2-4 weeks was 63 times higher than that of noncytotoxic CD3+ T cells (n = 6, 10.3-fold ranging from 0.8 to 35-fold). Thereafter, CD3+ T cells predominantly proliferated, and proliferation of CD3+ T cells (n = 5, 743-fold) for 5-6 weeks were 24 times higher than that of CD3-CD56+ NK cells (n = 5, 31-fold). Significant numbers of RCC-TIL became adherent to the surfaces of the bags several weeks after initiation of culture. These adherent TIL consisted of more CD3-CD56+ NK cells and exhibited higher cytotoxicity than did nonadherent TIL. Adherent RCC-TIL produced interferon (IFN)-gamma, while nonadherent TIL did not. These results suggest that initially cytotoxic CD3-CD56+ NK cells and, later, noncytotoxic CD3+ T cells proliferated in culture of RCC-TIL for adoptive therapy. These noncytotoxic TIL were primarily transferred to RCC patients, who also received cyclophosphamide, IL-2, and IFN-alpha. In contrast to RCC-TIL, IL-2-activated melanoma TIL consisting of all CD3+ T cells displayed modest levels of cytotoxicity, primarily restricted to autologous melanoma cells in all cases tested. The cytotoxic melanoma TIL were adoptively transferred to melanoma patients. Three of seven RCC patients responded to the adoptive therapy.</p>","PeriodicalId":77209,"journal":{"name":"Journal of immunotherapy : official journal of the Society for Biological Therapy","volume":"10 5","pages":"313-25"},"PeriodicalIF":0.0,"publicationDate":"1991-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1097/00002371-199110000-00003","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"12952230","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-2 with ex vivo activated killer cells: therapy of advanced non-small-cell lung cancer.","authors":"Z P Bernstein,&nbsp;M H Goldrosen,&nbsp;L Vaickus,&nbsp;N Friedman,&nbsp;H Watanabe,&nbsp;R Rahman,&nbsp;J Park,&nbsp;S G Arbuck,&nbsp;J Sweeney,&nbsp;D S Vesper","doi":"10.1097/00002371-199110000-00012","DOIUrl":"https://doi.org/10.1097/00002371-199110000-00012","url":null,"abstract":"<p><p>A phase II study was conducted to examine the efficacy of interleukin-2 (IL-2) with lymphokine-activated killer (LAK) cells as therapy for advanced non-small-cell lung carcinoma (NSCLC). IL-2 was administered at a fixed dose of 6 x 10(6) U/M2 per day as a 24 h continuous intravenous infusion (CIV) with LAK cells. Eleven patients were entered onto this study and six were evaluable. One patient had a near complete response of 18 months duration. Only two patients were able to complete the regimen without dose reduction. This regimen was poorly tolerated with pulmonary toxicity being the major problem. The partial responder was the only patient to undergo more than one course of therapy. IL-2/LAK therapy may have activity in NSCLC and further studies are warranted in this uniformly fatal disease. However, future studies will have to incorporate less toxic IL-2 regimens.</p>","PeriodicalId":77209,"journal":{"name":"Journal of immunotherapy : official journal of the Society for Biological Therapy","volume":"10 5","pages":"383-7"},"PeriodicalIF":0.0,"publicationDate":"1991-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1097/00002371-199110000-00012","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"12830274","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":"Phase II trial of recombinant DNA gamma-interferon in advanced colorectal cancer: a Southwest Oncology Group study.","authors":"T D Brown,&nbsp;P J Goodman,&nbsp;T Fleming,&nbsp;J S Macdonald,&nbsp;T O'Rourke,&nbsp;S A Taylor,&nbsp;J R Neefe,&nbsp;E Gaynor","doi":"10.1097/00002371-199110000-00011","DOIUrl":"https://doi.org/10.1097/00002371-199110000-00011","url":null,"abstract":"<p><p>Fifty evaluable patients with advanced colorectal cancer, but without prior chemotherapy or immunotherapy, were randomized to one of two schedules of recombinant gamma-interferon (rGIFN). Twenty-four evaluable patients received rGIFN as a 2-h intravenous infusion daily x 5 every other week at a starting dose of 4.0 x 10(6) IU/m2/day (arm I). Twenty-six evaluable patients received rGIFN as a 24-h continuous intravenous infusion daily x 5 every month at a starting dose of 2.6 x 10(6) IU/m2/day (arm II). Toxicities on both schedules included flu-like symptoms, fevers/rigors, nausea/vomiting, hypotension, leukopenia, hepatotoxicity, nephrotoxicity, diarrhea, anemia, confusion, and ileus. Toxicity appeared to be more severe on arm I. No antitumor responses were observed, with 95% confidence intervals of 0 to 14% for arm I and 0 to 13% for arm II.</p>","PeriodicalId":77209,"journal":{"name":"Journal of immunotherapy : official journal of the Society for Biological Therapy","volume":"10 5","pages":"379-82"},"PeriodicalIF":0.0,"publicationDate":"1991-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1097/00002371-199110000-00011","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"12952168","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":"Depressed ability of patients with melanoma or renal cell carcinoma to generate adherent lymphokine-activated killer cells.","authors":"P Sedlmayr,&nbsp;H Rabinowich,&nbsp;E M Elder,&nbsp;M S Ernstoff,&nbsp;J M Kirkwood,&nbsp;R B Herberman,&nbsp;T L Whiteside","doi":"10.1097/00002371-199110000-00005","DOIUrl":"https://doi.org/10.1097/00002371-199110000-00005","url":null,"abstract":"<p><p>Adherent lymphokine-activated killer (A-LAK) cells, selected from peripheral blood lymphocytes (PBL) of normal human donors by adherence to plastic, and cultured in the presence of interleukin 2 (IL-2), are highly enriched in CD3-CD56+ natural killer (NK) cells. These IL-2-activated NK cells proliferate extensively upon further culture in conditioned medium containing IL-2. In contrast, we previously found that with PBL of some patients with advanced cancer, the same procedure often failed to yield high enrichment of NK cells or substantial expansion in the numbers of these effector cells. To obtain sufficient numbers of A-LAK cells for adoptive immunotherapy in cancer patients, an improved method for generation of human A-LAK cells with irradiated mitogen-stimulated allogeneic PBL- or Epstein-Barr virus-transformed lymphoblastoid cell lines was introduced. In paired experiments, A-LAK cultures with feeder cells showed significantly enhanced IL-2-driven proliferation of A-LAK cells obtained from normal donors or patients with metastatic melanoma, renal cell carcinoma, and other types of solid cancers. The growth-promoting effect of feeders for A-LAK cells resulted in significantly improved expansion of CD3-CD56+ (NK) effector cells in A-LAK cultures established from normal donors. Cells in these cultures also had significantly higher levels of antitumor cytotoxicity against K562 and Daudi targets than did A-LAK cells grown in the absence of feeder cells. Enrichment in CD3-CD56+ cells and antitumor activity also occurred in patient A-LAK cultures supplemented with mitogen-stimulated feeder cells, but was not statistically significant. Overall, despite improved proliferation and CD3-CD56+ cell content of A-LAK cultures established in the presence of mitogen-activated feeder cells, only 39% (21/54) of patients tested generated A-LAK cells that would be judged acceptable for large-scale therapeutic use by criteria based on fold expansion and purity of A-LAK cells. These results suggest that in comparison to normal individuals, NK cells of many patients with advanced solid tumors are defective in their ability to respond by proliferation to IL-2 even in the presence of exogenously supplied growth factors.</p>","PeriodicalId":77209,"journal":{"name":"Journal of immunotherapy : official journal of the Society for Biological Therapy","volume":"10 5","pages":"336-46"},"PeriodicalIF":0.0,"publicationDate":"1991-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1097/00002371-199110000-00005","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"12952233","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":"Relapse after response to interleukin-2-based immunotherapy: patterns of progression and response to retreatment.","authors":"R M Sherry,&nbsp;S A Rosenberg,&nbsp;J C Yang","doi":"10.1097/00002371-199110000-00009","DOIUrl":"https://doi.org/10.1097/00002371-199110000-00009","url":null,"abstract":"<p><p>The initial site of disease relapse was identified for 79 patients with metastatic renal cell cancer (RCC), melanoma, colon cancer, or non-Hodgkin's lymphoma (NHL), who had achieved partial or complete responses to one of five IL-2-based immunotherapy regimens. The initial site of relapse was evenly distributed between pre-existing sites of disease (33%), new sites of disease (38%), or both (29%). There was no difference in the distribution of recurrences between patients with partial or complete responses. Fifty-one patients with prior complete or partial responses were retreated with additional IL-2-based therapy following tumor progression. Five of 51 patients retreated following relapse developed new partial responses. There were no complete responses. Three patients with NHL were retreated with IL-2 and LAK cells and all achieved a second response, while only 2 of 48 patients with other histologic diagnoses reresponded. It is concluded that after a partial or complete response to IL-2-based immunotherapy, patients who relapse do so equally at new and pre-existing sites of disease. A response to retreatment following tumor progression may be attained in patients with NHL, while a new response is unlikely for patients with melanoma and RCC.</p>","PeriodicalId":77209,"journal":{"name":"Journal of immunotherapy : official journal of the Society for Biological Therapy","volume":"10 5","pages":"371-5"},"PeriodicalIF":0.0,"publicationDate":"1991-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1097/00002371-199110000-00009","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"12952165","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":"Augmentation of natural killer cell activity in mice by Bru-Pel.","authors":"K Yabu,&nbsp;J S Youngner,&nbsp;D S Feingold,&nbsp;G Keleti,&nbsp;E Gorelik","doi":"10.1097/00002371-199110000-00002","DOIUrl":"https://doi.org/10.1097/00002371-199110000-00002","url":null,"abstract":"<p><p>The immunomodulatory and anti-tumor activity of Bru-Pel, an aqueous-ether extracted residue of Brucella abortus (strain 456), was investigated. Bru-Pel was administered to C57BL/6 mice intraperitoneally (i.p.) and tested for its effect on natural killer (NK) cell activity in spleen cells, liver, and peritoneal cavity. Three days after injecting 100 micrograms of Bru-Pel i.p., the cytotoxicity of spleen cells against YAC-1 target cells, assessed by LU20 increased by approximately two-fold and nonparenchymal cells of liver by greater than six-fold. The highest stimulatory effect of Bru-Pel was seen with peritoneal exudate cells, and 47-fold augmentation of NK cell activity was observed. Bru-Pel treatment made spleen, liver, and peritoneal exudate cells capable of lysing P815 mastocytoma cells, a tumor cell line highly resistant to lysis by unstimulated NK cells. In vivo, Bru-Pel inhibited the formation of experimental BL6 melanoma metastases; however, there was no significant effect on the eradication of established pulmonary metastatic lesions. These results demonstrate that in addition to its previously described macrophage-activating ability, Bru-Pel is highly efficient in stimulation of NK cell-mediated cytotoxicity in mice.</p>","PeriodicalId":77209,"journal":{"name":"Journal of immunotherapy : official journal of the Society for Biological Therapy","volume":"10 5","pages":"307-12"},"PeriodicalIF":0.0,"publicationDate":"1991-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1097/00002371-199110000-00002","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"12952229","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":"Autologous tumor-specific cytotoxicity of tumor-infiltrating lymphocytes derived from human renal cell carcinoma.","authors":"A S Koo,&nbsp;C L Tso,&nbsp;T Shimabukuro,&nbsp;C Peyret,&nbsp;J B deKernion,&nbsp;A Belldegrun","doi":"10.1097/00002371-199110000-00006","DOIUrl":"https://doi.org/10.1097/00002371-199110000-00006","url":null,"abstract":"<p><p>Conditions for generating and expanding cytotoxic tumor-specific, tumor-infiltrating lymphocytes (TIL) were studied to improve the efficacy of adoptive cancer immunotherapy. Thus, we have examined the growth and cytolytic patterns of bulk culture TIL from human renal cell carcinoma (RCC) cultured in low (20 U/ml) or high (1,000 U/ml) dose interleukin (IL)-2, with or without irradiated autologous tumor stimulation. By 55 days in culture, TIL grown in the presence of IL-2 without tumor stimulation lost their lytic activity, whereas those exposed to tumor stimulation maintained high levels of cytotoxicity against autologous and/or nonautologous tumor targets. Only TIL grown with low dose IL-2 and autologous tumor maintained long-term (over 4 months in culture) specific cytotoxicity against the autologous tumor, even upon cryopreservation and regrowth. These TIL were 88-97% and 80% positive for CD3 and CD8, with a persistent subset exhibiting CD4+ CD8+ double positive staining. Their specific cytotoxic activity was major histocompatibility complex Class I-restricted and inhibited by pretreating the TIL with anti-CD3 monoclonal antibody. TIL exposed to the four types of culture conditions, low or high dose IL-2, with or without irradiated autologous tumors, and exhibiting different lytic specificities, all expressed mRNA for interferon-gamma and tumor necrosis factor (TNF)-alpha, but not for IL-1-beta, IL-4, IL-6, and granulocyte-macrophage colony stimulating factor. The degree of TNF-alpha mRNA expression correlated with the degree of autologous tumor-specific cytotoxicity of these TIL. This initial report demonstrates that antigen-specific cytotoxicity against the autologous tumor does, in fact, exist within the RCC tumors.(ABSTRACT TRUNCATED AT 250 WORDS)</p>","PeriodicalId":77209,"journal":{"name":"Journal of immunotherapy : official journal of the Society for Biological Therapy","volume":"10 5","pages":"347-54"},"PeriodicalIF":0.0,"publicationDate":"1991-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1097/00002371-199110000-00006","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"12952234","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":"Phase I evaluation of recombinant tumor necrosis factor given in combination with recombinant interferon-gamma.","authors":"J W Smith,&nbsp;W J Urba,&nbsp;J W Clark,&nbsp;D L Longo,&nbsp;M Farrell,&nbsp;S P Creekmore,&nbsp;K C Conlon,&nbsp;H Jaffe,&nbsp;R G Steis","doi":"10.1097/00002371-199110000-00007","DOIUrl":"https://doi.org/10.1097/00002371-199110000-00007","url":null,"abstract":"<p><p>In light of in vitro and preclinical animal model data suggesting potential additive or synergistic antitumor effects from the combined use of interferon-gamma (IFN-gamma) and tumor necrosis factor-alpha (TNF-alpha), we conducted a phase I study employing escalating doses of each agent in 36 patients with solid tumors to determine the maximum tolerated dose (MTD). Patients were given an intramuscular (i.m.) injection of IFN-gamma, followed 5 min later by an i.m. injection of TNF-alpha, each agent in different sites, every other day for ten doses over 20 days. Patients received 10, 50, or 100 micrograms/m2 of each agent throughout the treatment course. No dose modifications were made. Patients suffering serious toxicity had therapy stopped and were considered to be off-study. All patients experienced fatigue, and 36% spent over half their time in bed on treatment days. Fever and chills were nearly universal. Mild to moderate elevations in serum transaminase levels were noted in 44% of patients, and 44% developed transient microscopic hematuria. Although 81% of patients had anorexia, only 17% of patients lost more than 3 kg of body wt during the 3 weeks of therapy. Because two of three patients receiving 100 micrograms/m2 of both agents developed serious toxicity (one fever greater than 105 degrees F, one thrombocytopenia 43,000/mm3), the MTD was established to be 100 micrograms/m2 of IFN-gamma plus 50 micrograms/m2 of TNF-alpha. The use of aspirin did not significantly alter the toxic effects of the agents. One patient with melanoma had a mixed response and one patient with mesothelioma transiently cleared his ascites of malignant cells.</p>","PeriodicalId":77209,"journal":{"name":"Journal of immunotherapy : official journal of the Society for Biological Therapy","volume":"10 5","pages":"355-62"},"PeriodicalIF":0.0,"publicationDate":"1991-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1097/00002371-199110000-00007","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"12952163","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}