Molecular biotherapy最新文献_第7页

Evaluation and clinical relevance of patient immune responses to intravenous therapy with murine monoclonal antibodies conjugated to adriamycin. 阿霉素偶联小鼠单克隆抗体静脉治疗对患者免疫反应的评价及其临床意义。

Molecular biotherapy Pub Date : 1991-03-01

B Avner, L Swindell, E Sharp, S K Liao, J R Ogden, B P Avner, R K Oldham

{"title":"Evaluation and clinical relevance of patient immune responses to intravenous therapy with murine monoclonal antibodies conjugated to adriamycin.","authors":"B Avner, L Swindell, E Sharp, S K Liao, J R Ogden, B P Avner, R K Oldham","doi":"","DOIUrl":"","url":null,"abstract":"A retrospective study was performed in order to examine the clinical relevance of human anti-murine antibodies (HAMA) to concurrent clinical events in 21 patients receiving intravenous therapy with cocktails of murine monoclonal antibodies conjugated to Adriamycin. In vivo tumor localization of the murine antibodies was also evaluated. Serum levels of HAMA, human-murine immune complexes (HMIC), and murine antibodies were measured using an automated fluorescence immunoassay. Immunohistochemical staining was performed on frozen sections of tumor biopsies from eight of the patients to examine the in vivo binding of the murine antibodies. The patients were divided into low, intermediate, and high antibody dose groups. The incidence of allergic symptoms (80%) and HAMA correlation (75%) were highest in the low dose group. Specific IgM HAMA was the most highly correlated with allergic reactions, being present in 61.5% of the allergic patients. Thirteen of the 21 patients studied (61.9%) developed allergic symptoms after one or more doses of the murine monoclonal antibody conjugates. The percentages of total antibody doses in the patients' sera at varying intervals post-infusion varied widely from patient to patient for any given time point and dose, suggesting complex factors in the distribution and clearance of the murine antibodies. All eight of the patients biopsied during or post-therapy exhibited tumor localization of the murine monoclonal antibodies. Six of the eight had concurrent HAMA in their sera. Thus, the presence of HAMA did not prevent in vivo localization of the murine antibodies in the target tumors.(ABSTRACT TRUNCATED AT 250 WORDS)","PeriodicalId":18809,"journal":{"name":"Molecular biotherapy","volume":"3 1","pages":"14-21"},"PeriodicalIF":0.0,"publicationDate":"1991-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"13225736","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}

引用次数: 0

Human monocytes inhibit lymphokine-activated killer cell expansion in vitro. 人单核细胞体外抑制淋巴因子激活的杀伤细胞扩增。

Molecular biotherapy Pub Date : 1991-03-01

P L Triozzi, W A Aldrich, J J Rinehart

{"title":"Human monocytes inhibit lymphokine-activated killer cell expansion in vitro.","authors":"P L Triozzi, W A Aldrich, J J Rinehart","doi":"","DOIUrl":"","url":null,"abstract":"Depleting monocytes from human peripheral blood mononuclear cells (PBMC) enhances the in vitro activation of lymphokine-activated killer (LAK) cells. To determine if monocytes also altered LAK-cell expansion, we evaluated two methods of depleting monocytes from PBMC: nylon wool adherence (NWA) and phenylalanine methyl ester (PME) treatment. Both methods of depleting monocytes enhanced interleukin-2 (IL-2) driven, LAK-cell expansion; LAK expansion, however, was significantly greater after depletion with NWA than after PME. LAK cytotoxicity after NWA and PME depletion was equivalent. The degree of monocyte depletion, determined by evaluating morphology and the number of Leu-M3 (CD14) positive cells, and the proliferation of Leu 19 (CD56), OKT-3 (CD3), Leu2 (CD8), and Leu 3a (CD4) positive cells was also equivalent. Exposure of IL-2 activated cells to PME did not alter their cytotoxic activity. However, sequential treatment of PBMC with NWA, then PME, or with PME and then NWA, resulted in reduced expansion. This reduction in expansion was similar to PBMC treated with PME alone. Exposure of PME-depleted cells to nylon wool or to supernatants obtained from cells adherent to nylon wool further decreased LAK expansion relative to cells treated with NWA alone. We conclude that even at relatively low cell density, human monocytes markedly inhibit LAK-cell expansion in IL-2 driven PBMC cultures. Further, depletion of monocytes by NWA adherence is more effective than by treatment with PME, possibly due to subtle cellular damage induced by this latter treatment. These findings have implication for the in vitro and in vivo generation of LAK-cells by IL-2.","PeriodicalId":18809,"journal":{"name":"Molecular biotherapy","volume":"3 1","pages":"22-5"},"PeriodicalIF":0.0,"publicationDate":"1991-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"13225676","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}

引用次数: 0

Comparison of biologic activities of synthetic lipopentapeptide analogs of bacterial lipoprotein in mice. 细菌脂蛋白脂五肽类似物在小鼠体内的生物活性比较。

Molecular biotherapy Pub Date : 1991-03-01

T Shimizu, Y Ohtsuka, Y Yanagihara, M Kurimura, M Takemoto, K Achiwa

{"title":"Comparison of biologic activities of synthetic lipopentapeptide analogs of bacterial lipoprotein in mice.","authors":"T Shimizu, Y Ohtsuka, Y Yanagihara, M Kurimura, M Takemoto, K Achiwa","doi":"","DOIUrl":"","url":null,"abstract":"Mitogenicity, lethal toxicity, induction of tumor necrotizing factor (TNF), and antitumor activity against Meth A fibrosarcoma of four chemically synthesized lipopentapeptide analogs, S-[2,3-bis(palmitoyloxy)-2R (designated as KAB-1), -2S(KAB-3)-propyl]-N-palmitoyl-(R)-cysteinyl-(S)-seryl- (S)-seryl-(S)-asparaginyl-(S)-alanine, S-[2,3-bis(palmitoyloxy)-2R(KAB-2), and -2S(KAB-4)-propyl]-N-[(2,2,2)-trichloroethoxycarbonyl]-(R)- cysteinyl-(S)-seryl-(S)-seryl-(S)-asparaginyl-(S)-alanine, of bacterial lipoprotein were investigated. These four analogs, as well as bacterial lipopolysaccharide (LPS) or synthetic Escherichia coli-type lipid A (506), were capable of increasing of [3H]thymidine into splenocytes of C3H/He mice. Although LPS and 506 did not exhibit the mitogenic activity in C3H/HeJ mice, KAB compounds showed remarkable mitogenicity. These analogs did not show the lethal toxicity at a high dose of 50 micrograms/mouse in galactosamine-loaded C57BL/6 mice. Peritoneal macrophages, stimulated with four analogs, caused the production of TNF which induces the L929 cell lysis in vitro. Twice, intravenous injections of 50 micrograms/mouse of these analogs showed weak growth inhibition of Meth A fibrosarcoma in BALB/c mice. The inhibitory effect of KAB-2 compound, which caused the strong TNF-induction among the four analogs, was the most potent. These results indicate that the biological activity of KAB-2 (R-configuration of the C-2 position in glycerol moiety with dipalmitoyl) is stronger than that of the other three analogs.","PeriodicalId":18809,"journal":{"name":"Molecular biotherapy","volume":"3 1","pages":"46-50"},"PeriodicalIF":0.0,"publicationDate":"1991-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"13225678","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}

引用次数: 0

Generation of MC-38 adenocarcinoma tumor-specific tumor infiltrating lymphocytes by murine anti-CD3 antibody and recombinant interleukin-2. 用小鼠抗cd3抗体和重组白细胞介素-2诱导MC-38腺癌肿瘤特异性肿瘤浸润淋巴细胞。

Molecular biotherapy Pub Date : 1991-03-01

R Lafreniere, K Borkenhagen, L D Bryant

{"title":"Generation of MC-38 adenocarcinoma tumor-specific tumor infiltrating lymphocytes by murine anti-CD3 antibody and recombinant interleukin-2.","authors":"R Lafreniere, K Borkenhagen, L D Bryant","doi":"","DOIUrl":"","url":null,"abstract":"The growth, in vitro cytolytic activity and phenotype of murine MC-38 adenocarcinoma tumor infiltrating lymphocytes (TILs) stimulated with anti-CD3 monoclonal antibody (mAb) and recombinant interleukin-2 (RIL-2) as compared to RIL-2 alone was investigated. When assayed for growth, anti-CD3 mAb + RIL-2 MC-38 TILs demonstrated an enhanced proliferative activity compared to RIL-2 alone (fold expansion, 16,228 and 365,713 compared to 112 and 5594, culture times: 55 and 118 days, experiments 1 and 2, respectively). TILs cultured with anti-CD3 mAb alone demonstrated little expansion (fold expansion 6 and 3, experiments 1 and 2, respectively). Early during culture, the anti-CD3 mAb + RIL-2 MC-38 expanded TILs demonstrated broad cytolytic activity (LU: day 17, against MCA-102: greater than 125, YAC-1: greater than 125, MC-38, greater than 125). This lytic picture reversed with time with increasing specificity demonstrated against MC-38 (LU: day 53, MCA-102: less than 1, YAC-1: less than 1, MC-38: 8). TILs expanded with RIL-2 alone demonstrated more lysis of the YAC-1 target and little lysis of the other targets.(ABSTRACT TRUNCATED AT 250 WORDS)","PeriodicalId":18809,"journal":{"name":"Molecular biotherapy","volume":"3 1","pages":"26-33"},"PeriodicalIF":0.0,"publicationDate":"1991-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"12992358","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}

引用次数: 0

A specific and potent immunotoxin composed of antibody ZME-018 and the plant toxin gelonin. 一种由ZME-018抗体和植物毒素凝胶蛋白组成的特异性强效免疫毒素。

Molecular biotherapy Pub Date : 1991-03-01

M G Rosenblum, J L Murray, L Cheung, R Rifkin, S Salmon, R Bartholomew

{"title":"A specific and potent immunotoxin composed of antibody ZME-018 and the plant toxin gelonin.","authors":"M G Rosenblum, J L Murray, L Cheung, R Rifkin, S Salmon, R Bartholomew","doi":"","DOIUrl":"","url":null,"abstract":"Murine monoclonal antibody ZME-018 recognizes a 240 Kda glycoprotein present on the surface of most human melanoma cells and on over 80% of human biopsy specimens tested. Gelonin is a ribosome-inactivating plant toxin similar in nature and rivaling the activity of ricin A chain. ZME-018 was coupled to purified gelonin using the reagents SPDP and 2-iminothiolane. The ZME-gelonin conjugate was purified by S-300 Sephacryl and Blue Sepharose chromatography, removing unreacted gelonin and antibody, respectively. PAGE analysis showed that ZME was coupled to 1, 2, or 3 gelonin molecules. The ZME-gelonin conjugate was 10(6)-fold more active than gelonin itself in inhibiting the growth of log-phase human melanoma cells in culture. The immunoconjugate was not cytotoxic to antigen negative T-24 (human bladder carcinoma) cells. Treatment of melanoma cells with recombinant IFN-alpha or TNF substantially augmented the cytotoxicity of the immunoconjugate while treatment with IFN-gamma had a minor effect. Using the human tumor colony assay of melanoma cells obtained from fresh biopsy specimens, greater than 90% growth suppression was observed in 2 of 4 samples tested at a concentration of 250 ng/ml. In addition, 25% growth suppression was observed with a third sample tested, and no growth suppression was observed in 1 sample. Thus, clonogenic melanoma cells are sensitive in vitro to the cytotoxic activity of this immunotoxin at concentrations which we presume are pharmacologically relevant.","PeriodicalId":18809,"journal":{"name":"Molecular biotherapy","volume":"3 1","pages":"6-13"},"PeriodicalIF":0.0,"publicationDate":"1991-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"13066437","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}

引用次数: 0

Is informed consent a function of who pays? 知情同意是谁付钱的一个功能吗?

Molecular biotherapy Pub Date : 1991-03-01

R K Oldham

引用次数: 0

Studies of the effect of acemannan on retrovirus infections: clinical stabilization of feline leukemia virus-infected cats. 阿赛曼南对逆转录病毒感染的影响研究:猫白血病病毒感染猫的临床稳定。

Molecular biotherapy Pub Date : 1991-03-01

M A Sheets, B A Unger, G F Giggleman, I R Tizard

引用次数: 0

Modulation of tumor-induced angiogenesis by proteins of extracellular matrix. 细胞外基质蛋白对肿瘤诱导血管生成的调节作用。

Molecular biotherapy Pub Date : 1991-03-01

A M Eiján, L Davel, S Oisgold-Dagá, E S de Lustig