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Induction of 2'-5' oligoadenylate synthetase during interferon treatment of chronic myelogenous leukemia. 干扰素治疗慢性骨髓性白血病诱导2′-5′低聚腺苷酸合成酶的研究。
Molecular biotherapy Pub Date : 1992-06-01
T Moritz, B Weissmann, B Grünewald, H Hust, G Kummer, N Niederle
{"title":"Induction of 2'-5' oligoadenylate synthetase during interferon treatment of chronic myelogenous leukemia.","authors":"T Moritz,&nbsp;B Weissmann,&nbsp;B Grünewald,&nbsp;H Hust,&nbsp;G Kummer,&nbsp;N Niederle","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Activity of the interferon-induced enzyme 2'-5' oligoadenylate synthetase (2-5 OAS) was measured in peripheral blood mononuclear cells (PBMCs) and serum of patients with chronic phase Ph'-positive chronic myelogenous leukemia (CML) treated with interferon-alpha (IFN-alpha) (4 x 10(6) IU/m2) alone or in combination with 50 micrograms IFN-gamma. At the beginning of IFN therapy, marked elevation of 2-5 OAS titers was detected in PBMCs (pretreatment 0.03-1.62, median 0.2; during treatment 0.8-13.14, median 4.31; 22 patients studied) and in serum (pretreatment 21-156 pmol/dl, median 62; during treatment 532-1740 pmol/dl, median 800; eight patients studied). However, 2-5 OAS titers were not related to clinical outcome or IFN therapy and also during IFN resistance elevated 2-5 OAS activity in PBMCs (median 3.45; range 1.05-13.14; 11 patients studied) were detected. These data argue against direct involvement of the 2-5 OAS system in the therapeutic effect of IFN in CML. However, 2-5 OAS titers in PBMCs or serum appear to be a reliable control of biologically active IFN therapy.</p>","PeriodicalId":18809,"journal":{"name":"Molecular biotherapy","volume":"4 2","pages":"97-102"},"PeriodicalIF":0.0,"publicationDate":"1992-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"12553139","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
Biologic and therapeutic efficacy of mafosfamide in patients with metastatic renal cell carcinoma. 麻环素治疗转移性肾细胞癌的生物学及治疗效果。
Molecular biotherapy Pub Date : 1992-06-01
A Schomburg, T Menzel, M Hadam, S Duensing, A Körfer, H Kirchner, H Poliwoda, J Atzpodien
{"title":"Biologic and therapeutic efficacy of mafosfamide in patients with metastatic renal cell carcinoma.","authors":"A Schomburg,&nbsp;T Menzel,&nbsp;M Hadam,&nbsp;S Duensing,&nbsp;A Körfer,&nbsp;H Kirchner,&nbsp;H Poliwoda,&nbsp;J Atzpodien","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>It is well known that oxazaphosphorines [e.g., cyclophosphamide and 4-hydroperoxycyclophosphamide (mafosfamide)] are potent immunosuppressive agents. Under the proper conditions, they can potentiate immune responses as well. Immunomodulation represents a major breakthrough in the management of chemotherapy-resistant tumors. Thus, we evaluated the clinical and laboratory sequelae of low to intermediate doses (100-1000 mg/m2) of mafosfamide administered to 16 patients. Four weeks after therapy, one patient had a complete remission, eight patients presented with stable disease, and seven patients did not respond. Clinical and laboratory toxicity was mild and totally reversible, and therapy was well tolerated in all patients. Analyses of phenotypic cell surface antigens on circulating peripheral blood mononuclear cells showed inconsistent alterations of the CD4/CD8 ratio, initial depletion with later rebound of CD8+ cells, increase of CD20+ cells, and a mafosfamide dose-dependent regulation of natural killer-like cells as characterized by CD16 and CD56 positivity. Cell-mediated cytotoxicity against K562 target cells peaked 1 day after therapy and was most pronounced in patients who had received 300 mg/m2 mafosfamide, whereas cytotoxicity against Daudi targets was essentially unchanged, consistent with an increase in natural killing activity without augmentation of lymphokine activated killing. We conclude that mafosfamide administration at low to intermediate doses can be performed with good safety and tolerance; immunophenotypic analyses and cytotoxicity assays showed most pronounced alterations in patients receiving low doses of mafosfamide. These observations support the use of mafosfamide in the attempt to augment antitumor immune responses.</p>","PeriodicalId":18809,"journal":{"name":"Molecular biotherapy","volume":"4 2","pages":"58-65"},"PeriodicalIF":0.0,"publicationDate":"1992-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"12683461","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
Interleukin-2 increases the antibody response in patients receiving autologous intralymphatic tumor cell vaccine immunotherapy. 白细胞介素-2增加了接受自体淋巴内肿瘤细胞疫苗免疫治疗的患者的抗体反应。
Molecular biotherapy Pub Date : 1992-06-01
T W Williams, J M Yanagimoto, A Mazumder, C L Wiseman
{"title":"Interleukin-2 increases the antibody response in patients receiving autologous intralymphatic tumor cell vaccine immunotherapy.","authors":"T W Williams,&nbsp;J M Yanagimoto,&nbsp;A Mazumder,&nbsp;C L Wiseman","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>The production of tumor-binding antibodies was studied in a group of cancer patients undergoing active specific immunotherapy with irradiated, cholesterol-treated, cell culture-derived autologous tumor cells injected by the intralymphatic route. Fifteen patients were analyzed: nine patients (four melanoma, one breast, one sarcoma, one colon, and one undifferentiated cancer) received three injections of 10 to 15 x 10(6) tumor cells, spaced 2 weeks apart, and six patients (two melanoma, two renal, one breast, and one colon cancer) received tumor cells admixed with 3 x 10(6) U recombinant interleukin-2 (IL-2) (Proleukin, Cetus, Emeryville, CA, USA) plus a 10-day intravenous infusion of 15 x 10(6) U/kg/day IL-2 after each immunization. Serum antibody binding to autologous tumor cells was measured at 2 and 4 weeks after initiation of therapy using an enzyme-linked immunosorbent assay with patient serum being added to adherent tumor cells bound to 96-well microtiter plates. After 4 weeks, we found a significant difference (0.02 less than P less than 0.04) in serum titer in the group receiving IL-2 (33% mean increase) compared with the non-IL-2 group (8% mean increase). Although neither group showed clinical improvement in response to the therapy, the results clearly demonstrated the efficacy of IL-2 in augmenting patient antibody response to autologous intralymphatic tumor cell immunization.</p>","PeriodicalId":18809,"journal":{"name":"Molecular biotherapy","volume":"4 2","pages":"66-9"},"PeriodicalIF":0.0,"publicationDate":"1992-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"12683462","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
Genetic engineering of anticolorectal carcinoma Fv molecule in myeloma cells. 骨髓瘤细胞中抗结直肠癌Fv分子的基因工程研究。
Molecular biotherapy Pub Date : 1992-06-01
J Xiang
{"title":"Genetic engineering of anticolorectal carcinoma Fv molecule in myeloma cells.","authors":"J Xiang","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>The anti-TAG72 Fv molecule composed of a heterodimer of both heavy- and light-chain variable domains was produced by the construction of the expression vector mpSV2neo-EP1-Fv72.3. This vector contained the neo gene as a selection marker, the murine immunoglobulin heavy chain promoter (P1), enhancer (E), the SV40 polyadenylation signal region, and the murine cDNA fragments of VH and VL regions amplified and cloned directly from the B72.3 hybridoma RNA by the polymerase chain reaction technique. Termination codons were introduced into the 3' end of both VH and VL regions. The expression vector was transfected into the SP2/0 cell line. The Fv72.3 molecules were purified by the rabbit anti-B72.3 idiotype antibody affinity column, and retained the binding reactivity for the TAG72 antigen. The small size of Fv72.3 molecule (25 kD) makes it attractive for structural studies and immunodetection of cancers.</p>","PeriodicalId":18809,"journal":{"name":"Molecular biotherapy","volume":"4 2","pages":"70-6"},"PeriodicalIF":0.0,"publicationDate":"1992-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"12685316","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
Modulation of hematologic and immunologic effects of high dose chemotherapy by interleukin-2 in a murine tumor model. 白细胞介素-2在小鼠肿瘤模型中高剂量化疗对血液学和免疫效应的调节。
Molecular biotherapy Pub Date : 1992-06-01
J J Rinehart, P L Triozzi, M H Lee, W Aldrich, D Young
{"title":"Modulation of hematologic and immunologic effects of high dose chemotherapy by interleukin-2 in a murine tumor model.","authors":"J J Rinehart,&nbsp;P L Triozzi,&nbsp;M H Lee,&nbsp;W Aldrich,&nbsp;D Young","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>To determine if intensive chemotherapy consisting of cyclophosphamide (C), etoposide (E), and cisplatin (P) (CEP) may be usefully combined with recombinant human interleukin-2 (rhIL-2), we examined a murine tumor model designed to approximate a common clinical situation: macroscopic, drug-resistant cancer. Using C57BL/6 mice with extensive tumor burden 10 days after intravenous B16 melanoma cell injection, we observed (1) C, E, and P synergize to enhance survival but do not cure mice at the highest tolerable dose (C = 200 mg/kg, E = 60 mg/kg, and P = 3 mg/kg); (2) rhIL-2 at 3 x 10(5) U (subcutaneously) daily for 4 days administered 10-18 days after B16 injection significantly improves survival; (3) CEP plus rhIL-2 is more effective than CEP alone only when rhIL-2 is administered before CEP; (4) CEP suppresses IL-2-induced lymphokine-activated killer cell activity in the spleen; and (5) rhIL-2 protects mice incompletely from the immunologic and hematologic suppression of CEP. Our results suggest that intensive chemotherapy combined with rhIL-2 may be beneficial. The success of any such combination may be schedule dependent.</p>","PeriodicalId":18809,"journal":{"name":"Molecular biotherapy","volume":"4 2","pages":"77-82"},"PeriodicalIF":0.0,"publicationDate":"1992-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"12685317","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
Metastases to skeletal muscles and interferon treatment. 转移到骨骼肌和干扰素治疗。
Molecular biotherapy Pub Date : 1992-06-01
O Merimsky, M Inbar, S Chaitchik
{"title":"Metastases to skeletal muscles and interferon treatment.","authors":"O Merimsky,&nbsp;M Inbar,&nbsp;S Chaitchik","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Blood-borne metastases to a skeletal muscle are rare and may originate in various primary tumors. Recurrent solitary metastasis of renal cell carcinoma, and metastatic lesion as part of disseminated malignant melanoma in skeletal muscles are reported in two patients. In both cases interferon treatment with or without chemotherapy failed in arresting the disease.</p>","PeriodicalId":18809,"journal":{"name":"Molecular biotherapy","volume":"4 2","pages":"95-6"},"PeriodicalIF":0.0,"publicationDate":"1992-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"12685320","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
Effect of colony-stimulating factors on number and function of circulating monocytes in normal dogs. 集落刺激因子对正常犬循环单核细胞数量和功能的影响。
Molecular biotherapy Pub Date : 1992-03-01
I D Kurzman, E G MacEwen, C Broderick, P Witte
{"title":"Effect of colony-stimulating factors on number and function of circulating monocytes in normal dogs.","authors":"I D Kurzman,&nbsp;E G MacEwen,&nbsp;C Broderick,&nbsp;P Witte","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Recombinant human granulocyte-macrophage colony-stimulating factor (rhuGM-CSF) and recombinant canine granulocyte colony-stimulating factor (rcG-CSF) were administered to normal dogs, and effect on monocyte number and function was evaluated. rhuGM-CSF, administered for 14 days, induced a 2.5-fold increase in monocyte counts on day 3. Leukocytes increased two-fold after 1 day. Counts peaked on day 11, then declined, approaching pretreatment counts by day 15. On day 7, in vivo monocyte cytostasis activity was significantly enhanced, and declined on day 14. rcG-CSF induced a 4.5-fold increase in monocyte counts on day 3. Leukocyte counts increased three-fold after 1 day. Increased counts were maintained for 69 days, at which time treatment was discontinued. There was no effect of rcG-CSF on in vivo monocyte cytostasis activity on days 7 and 14.</p>","PeriodicalId":18809,"journal":{"name":"Molecular biotherapy","volume":"4 1","pages":"29-33"},"PeriodicalIF":0.0,"publicationDate":"1992-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"12550562","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
Antitumor activity of recombinant human tumor necrosis factor in combination with hyperthermia against heterotransplanted human prostatic carcinoma and its lymph node metastasis in nude mice. 重组人肿瘤坏死因子联合热疗对裸鼠异移植人前列腺癌及其淋巴结转移的抗肿瘤活性。
Molecular biotherapy Pub Date : 1992-03-01
T Hachiya, K Okada, A Sakurai, N Satomi, K Haranaka
{"title":"Antitumor activity of recombinant human tumor necrosis factor in combination with hyperthermia against heterotransplanted human prostatic carcinoma and its lymph node metastasis in nude mice.","authors":"T Hachiya,&nbsp;K Okada,&nbsp;A Sakurai,&nbsp;N Satomi,&nbsp;K Haranaka","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>The antitumor activity of recombinant human tumor necrosis factor (rhTNF) against heterotransplanted human prostatic carcinoma (PC-3) and spontaneous lymphatic tumor metastasis was studied in vivo. The spontaneous lymphatic metastasis of PC-3 tumor was found in approximately 50% of cases. Significant antitumor activity was observed with repeated intratumoral administration of a large dose of rhTNF, not only on the subcutaneous tumor xenografts but also on the lymph node metastases. Strong antitumor activity could be achieved even with the intratumoral administration of a small dose of rhTNF in combination with mild hyperthermia on either the transplanted tumors or on the metastatic tumors.</p>","PeriodicalId":18809,"journal":{"name":"Molecular biotherapy","volume":"4 1","pages":"34-9"},"PeriodicalIF":0.0,"publicationDate":"1992-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"12793495","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
Production of hybrid bispecific antibody recognizing human colorectal carcinoma and CD3 antigen. 识别人结直肠癌和CD3抗原的杂交双特异性抗体的制备。
Molecular biotherapy Pub Date : 1992-03-01
J Xiang, Z Pan, S Attah-Poku, L Babiuk, Y Zhang, E Liu
{"title":"Production of hybrid bispecific antibody recognizing human colorectal carcinoma and CD3 antigen.","authors":"J Xiang,&nbsp;Z Pan,&nbsp;S Attah-Poku,&nbsp;L Babiuk,&nbsp;Y Zhang,&nbsp;E Liu","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>The present study reports on the use of gene transfer by vector DNA in the generation of hybrid hybridoma, the quadroma secreting the hybrid bispecific antibody. A quadroma B72.3neo/OKT3gpt was simply derived from the fusion of two hybridoma cell lines, B72.3 and OKT3, tagged with vector DNA mpSV2neo and mpSV2gpt, respectively, and selected in the media containing both G418 and mycophenolic acid. The hybrid bispecific antibody B72.3/OKT3 was purified from the quadroma ascites by the use of hydroxylapatite column on high-pressure liquid chromatography. This bispecific antibody contained one binding site for the TAG72 antigen on OVCAR3 tumor cells and the other binding site for the CD3 molecule on human T cells. It was able to target human T lymphocytes to significantly lyse the human ovarian cancer cells and may therefore be useful in immunotherapy of cancer.</p>","PeriodicalId":18809,"journal":{"name":"Molecular biotherapy","volume":"4 1","pages":"15-23"},"PeriodicalIF":0.0,"publicationDate":"1992-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"12558235","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
Peer review. 同行审查。
Molecular biotherapy Pub Date : 1992-03-01
R K Oldham
{"title":"Peer review.","authors":"R K Oldham","doi":"","DOIUrl":"","url":null,"abstract":"","PeriodicalId":18809,"journal":{"name":"Molecular biotherapy","volume":"4 1","pages":"2-3"},"PeriodicalIF":0.0,"publicationDate":"1992-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"12793493","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
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