Cancer biotherapy最新文献_第9页

Report on the 8th Maimonides conference on cancer research, February 22-26, Ein Gedi, Israel. 第8届迈蒙尼德癌症研究会议报告，2月22-26日，以色列Ein Gedi。

Cancer biotherapy Pub Date : 1993-01-01 DOI: 10.1089/cbr.1993.8.181

G Pawelec

引用次数: 1

What's the score? 比分是多少?

Cancer biotherapy Pub Date : 1993-01-01 DOI: 10.1089/cbr.1993.8.187

R K Oldham

引用次数: 4

The impact of interleukin-2 on survival in renal cancer: a multivariate analysis. 白细胞介素-2对肾癌患者生存的影响:一项多变量分析。

Cancer biotherapy Pub Date : 1993-01-01 DOI: 10.1089/cbr.1993.8.275

M Jones, T Philip, P Palmer, H von der Maase, J Vinke, P Elson, C R Franks, P Selby

{"title":"The impact of interleukin-2 on survival in renal cancer: a multivariate analysis.","authors":"M Jones, T Philip, P Palmer, H von der Maase, J Vinke, P Elson, C R Franks, P Selby","doi":"10.1089/cbr.1993.8.275","DOIUrl":"https://doi.org/10.1089/cbr.1993.8.275","url":null,"abstract":"The purpose of this analysis was to compare the survival of patients with advanced renal carcinoma treated with intravenous recombinant interleukin-2 to the survival of matched patients taken from the large and well characterised database of the Eastern Cooperative Oncology Group (ECOG). Recombinant interleukin-2 (rIL-2) given by continuous intravenous infusion was used to treat 387 patients with advanced adenocarcinoma of the kidney in five multi-centre studies and 327 of these patients fulfilled the study eligibility criteria and were evaluable for response, toxicity and survival. The survival of patients treated with rIL-2 was compared in a multi-variate survival analysis taking account of all identified prognostic factors to 390 control patients receiving chemotherapy derived from the database. Thirteen patients treated with rIL-2 achieved a complete remission of their disease and 32 a partial remission giving an overall response rate of 14%. Remissions were durable with a median duration of 357 days for partial remissions and a median duration in excess of 926 days for complete remissions. Most patients experienced fever or mild to moderate hypotension and other toxicities are described. However, only 11 patients required admission to intensive care and in only five cases was this judged to be due to treatment toxicity. There were three deaths judged to be probably due to treatment toxicity. rIL-2 treatment was associated with significantly prolonged survival compared to the ECOG control patients. Patients with good prognostic features appeared to have a greater survival benefit from rIL-2 than those with poor prognostic features. This analysis provides the first evidence that rIL-2 prolongs survival in patients with advanced renal cancer but cannot provide proof which should be sought in randomised prospective trials drawing on the hypotheses generated herein.","PeriodicalId":79322,"journal":{"name":"Cancer biotherapy","volume":"8 4","pages":"275-88"},"PeriodicalIF":0.0,"publicationDate":"1993-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1089/cbr.1993.8.275","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"18803807","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: 85

A phase I escalating-dose safety, dosimetry and efficacy study of radiolabeled monoclonal antibody LYM-1. 放射标记单克隆抗体LYM-1的I期递增剂量安全性、剂量学和疗效研究。

Cancer biotherapy Pub Date : 1993-01-01 DOI: 10.1089/cbr.1993.8.3

T Kuzel, S T Rosen, A M Zimmer, E A Silverstein, S Spies, S L Saletan, M E Norvitch, M Birkhofer, D Shochat, A F LoBuglio

{"title":"A phase I escalating-dose safety, dosimetry and efficacy study of radiolabeled monoclonal antibody LYM-1.","authors":"T Kuzel, S T Rosen, A M Zimmer, E A Silverstein, S Spies, S L Saletan, M E Norvitch, M Birkhofer, D Shochat, A F LoBuglio","doi":"10.1089/cbr.1993.8.3","DOIUrl":"https://doi.org/10.1089/cbr.1993.8.3","url":null,"abstract":"Thirteen patients with relapsed or refractory Non-Hodgkin's Lymphoma were treated with 131I-Lym-1 during the course of a dose escalation trial. Principal aims were to establish the maximum tolerated single dose (MTD), as well as to assess clinical and dosimetric effects of the MTD. Patients were eligible if > 25% of tumor cells bound Lym-1 on immunohistochemistry, stain intensity was +2/4 or greater and human anti-mouse antibody (HAMA) assay was negative. Radioimmunotherapy was performed with escalating doses at levels of 50 mCi, 65 mCi/m2 and 80 mCi/m2 (50-139 mCi total). Patients were eligible for retreatment after 6-10 weeks if there was no severe toxicity, their disease was at least stable and HAMA remained negative. Three were retreated. Four have achieved partial responses which lasted 11, 11, 18 and 22 weeks. Acute toxicities included rigors (69%), fever (62%), nausea (46%), vomiting (46%), pruritus (23%), urticaria (23%), chest pain (23%) and bronchospasm (15%). HAMA developed in 3 patients. Myelosuppression, manifested as thrombocytopenia and neutropenia, was dose-limiting and defined the single dose MTD at 65 mCi/m2. Plasma radioactivity clearance was biphasic, with a 0.9 hr alpha-T1/2 and a 19.8 hr beta-T1/2. At completion of Lym-1 infusion, a mean of 45% of the injected dose was recoverable in the circulation. Images obtained within the first 2 hours indicated mean hepatic and splenic uptake was 29% and 11%, respectively. Radiation absorbed doses to tumor ranged from 18-61 rads; mean doses to whole body ranged from 17 to 71 rads.","PeriodicalId":79322,"journal":{"name":"Cancer biotherapy","volume":"8 1","pages":"3-16"},"PeriodicalIF":0.0,"publicationDate":"1993-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1089/cbr.1993.8.3","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"18812886","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: 30

Construction and purification of domain-deleted immunoglobulin variants of the recombinant/chimeric B72.3 (y1) monoclonal antibody. 重组/嵌合B72.3 (y1)单克隆抗体结构域缺失免疫球蛋白变体的构建与纯化

Cancer biotherapy Pub Date : 1993-01-01 DOI: 10.1089/cbr.1993.8.95

B Calvo, S V Kashmiri, P Hutzell, P H Hand, D C Slavin-Chiorini, J Schlom, S Zaremba

{"title":"Construction and purification of domain-deleted immunoglobulin variants of the recombinant/chimeric B72.3 (y1) monoclonal antibody.","authors":"B Calvo, S V Kashmiri, P Hutzell, P H Hand, D C Slavin-Chiorini, J Schlom, S Zaremba","doi":"10.1089/cbr.1993.8.95","DOIUrl":"https://doi.org/10.1089/cbr.1993.8.95","url":null,"abstract":"Chimeric antibodies have been produced against a pancarcinomic tumor associated antigen, TAG-72, by fusing the genes for the variable region of mouse MAb B72.3 to the genes for the constant region of human IgG. In our efforts to optimize the pharmacokinetics of plasma clearance and the efficiency of tumor localization and penetrance of cB72.3, we have now developed truncated versions of immunoglobulin heavy chains. The domain-deleted antibodies are produced by transfecting cells that produce chimeric kappa chains with expression vectors that encode chimeric heavy chains lacking the sequences that encode the CH2 domain, CH3 domain, or both. Despite the absence of these domains, the transfectomas secrete H2L2 tetramers with appropriate antigenic specificity. All the domain-deleted immunoglobulins can be purified by chromatography on Protein G Sepharose which binds to a site on the Fab region that is retained in the domain-deleted antibodies. The CH2CH3 domain-deleted immunoglobulin produced in cell culture is analogous in size to enzymatically produced F(ab')2.","PeriodicalId":79322,"journal":{"name":"Cancer biotherapy","volume":"8 1","pages":"95-109"},"PeriodicalIF":0.0,"publicationDate":"1993-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1089/cbr.1993.8.95","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"18535966","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: 8

Sustained oral indomethacin and ranitidine with intermittent continuous infusion interleukin-2 in advanced renal cell carcinoma. 持续口服吲哚美辛和雷尼替丁并间歇持续输注白介素-2治疗晚期肾细胞癌。

Cancer biotherapy Pub Date : 1993-01-01 DOI: 10.1089/cbr.1993.8.229

W C Mertens, V H Bramwell, D Banerjee, F Gwadry-Sridhar, N al-Mutter, R S Parhar, P K Lala

{"title":"Sustained oral indomethacin and ranitidine with intermittent continuous infusion interleukin-2 in advanced renal cell carcinoma.","authors":"W C Mertens, V H Bramwell, D Banerjee, F Gwadry-Sridhar, N al-Mutter, R S Parhar, P K Lala","doi":"10.1089/cbr.1993.8.229","DOIUrl":"https://doi.org/10.1089/cbr.1993.8.229","url":null,"abstract":"Experimental work in murine models has shown that, during the development of tumors, prostaglandin E2 produced by host macrophages inactivates natural killer cells and suppresses lymphokine-activated killer (LAK) cell development. Chronic indomethacin therapy when combined with interleukin-2 (IL-2) can totally eradicate experimental lung metastases in these models. A phase II trial was performed to study the clinical efficacy of chronic indomethacin and intermittent IL-2 therapy in patients with advanced renal cell carcinoma. Patients were placed on indomethacin and ranitidine orally at least one week prior to commencing therapy with IL-2. IL-2 was given by continuous infusion for three courses, each consisting of 5 days of treatment with 6 days of rest. Initial dose of IL-2 was 18.0 x 10(6) IU/m2/day for the first course with escalation to 27.0 x 10(6) IU/m2/day for the second and 36.0 x 10(6) IU/m2/day for the third course, if toxicity allowed. Patients were admitted to a general oncology ward for therapy with IL-2, and vasopressor agents were not used. Thirty-two patients were eligible, with 7 patients withdrawing early from the study. Twenty-five patients went on to receive at least one course of IL-2. Two complete and three partial responses were seen for an objective response rate of 5/25 (20%) for eligible and treated patients or 5/32 (16%) for all patients entered onto the study, regardless of treatment status. The response rate to this regimen is comparable with other high dose IL-2 regimens in renal cell carcinoma, including those employing adoptive therapy with lymphokine-activated killer cells.","PeriodicalId":79322,"journal":{"name":"Cancer biotherapy","volume":"8 3","pages":"229-33"},"PeriodicalIF":0.0,"publicationDate":"1993-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1089/cbr.1993.8.229","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"18803289","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: 14

Protective effect of gypenosides against oxidative stress in phagocytes, vascular endothelial cells and liver microsomes. 绞股蓝皂苷对吞噬细胞、血管内皮细胞和肝微粒体氧化应激的保护作用。

Cancer biotherapy Pub Date : 1993-01-01 DOI: 10.1089/cbr.1993.8.263

L Li, L Jiao, B H Lau

引用次数: 76

Subcutaneous recombinant interleukin-2 and alpha-interferon in patients with advanced renal cell carcinoma: results of a multicenter Phase II Study. 晚期肾细胞癌患者皮下重组白细胞介素-2和α -干扰素:一项多中心II期研究的结果

Cancer biotherapy Pub Date : 1993-01-01 DOI: 10.1089/cbr.1993.8.289

J Atzpodien, H Kirchner, P de Mulder, H Bodenstein, T Oliver, P A Palmer, C R Franks, H Poliwoda

{"title":"Subcutaneous recombinant interleukin-2 and alpha-interferon in patients with advanced renal cell carcinoma: results of a multicenter Phase II Study.","authors":"J Atzpodien, H Kirchner, P de Mulder, H Bodenstein, T Oliver, P A Palmer, C R Franks, H Poliwoda","doi":"10.1089/cbr.1993.8.289","DOIUrl":"https://doi.org/10.1089/cbr.1993.8.289","url":null,"abstract":"A phase II multiinstitutional clinical trial was conducted to evaluate the safety and efficacy of the subcutaneous outpatient administration of recombinant human interleukin-2 and alpha-interferon in patients with progressive metastatic renal cell carcinoma. One hundred and forty-five patients were entered on this study between October 1989 and May 1991. Among 134 patients evaluable for treatment response, there were six complete (4.5%) and twenty partial (14.9%) responders, with an overall response rate of 19.4% (95% confidence interval, 13-26%). The median duration of complete remissions was 228 (range 51(+)-520+) days; the median duration of partial tumor regressions was calculated at 226 (range 112-473+) days. The overall median survival from start of therapy was 14.2 (range 1-23+) months. Fever, chills and general fatigue occurred in the majority of patients treated and were measured at grade II, III and IV in up to 55%, 24% and 3% of all evaluable patients, respectively. Three patients each developed grade III hypotension, dyspnea and diarrhea; two patients each had grade III and grade IV elevations of alkaline phosphatase; two and one patients respectively, exhibited grade III anemia and grade IV thrombocytopenia; two patients experienced severe cutaneous toxicity. The majority of patients received treatment in the outpatient setting. In summary, the outpatient use of subcutaneous interleukin-2 and alpha-interferon was effective in patients with advanced metastatic renal cell carcinoma; it was associated with less toxicity and thus, could improve the therapeutic index of interleukin-2 based biologic therapy when compared against high dose intravenous therapy.","PeriodicalId":79322,"journal":{"name":"Cancer biotherapy","volume":"8 4","pages":"289-300"},"PeriodicalIF":0.0,"publicationDate":"1993-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1089/cbr.1993.8.289","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"18803808","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: 13

Fundamentally flawed? 根本性的缺陷呢?

Cancer biotherapy Pub Date : 1993-01-01 DOI: 10.1089/cbr.1993.8.111

R K Oldham

引用次数: 5

The tyrosine residue at position 97 in the VH CDR3 region of a mouse/human chimeric anti-colorectal carcinoma antibody contributes hydrogen bonding to the TAG72 antigen. 小鼠/人嵌合抗结直肠癌抗体VH CDR3区97位酪氨酸残基与TAG72抗原形成氢键。

Cancer biotherapy Pub Date : 1993-01-01 DOI: 10.1089/cbr.1993.8.253

J Xiang, E Liu, L T Delbaere, Z Chen, X Luo, Y Qi, C Rathgeber

{"title":"The tyrosine residue at position 97 in the VH CDR3 region of a mouse/human chimeric anti-colorectal carcinoma antibody contributes hydrogen bonding to the TAG72 antigen.","authors":"J Xiang, E Liu, L T Delbaere, Z Chen, X Luo, Y Qi, C Rathgeber","doi":"10.1089/cbr.1993.8.253","DOIUrl":"https://doi.org/10.1089/cbr.1993.8.253","url":null,"abstract":"One amino acid, tyrosine at position 96 and 97 in the VH CDR3 region of a mouse/human chimeric anti-TAG72 antibody cB72.3m4 was substituted by the phenylalanine residue and by a number of amino acids from different amino acid groups by the site-directed mutagenesis technique. The expression vector mpSV2neo-EP1-Vm11-16C1 containing mutant VH region fragments (Vm11-16) as well as the immunoglobulin enhances (E), promoter (P1) and the human genomic C1 region fragments, were transfected into a heavy-chain-loss mutant cell line B72.3Mut(K), respectively. Mutant chimeric cB72.3m11-16 antibodies were purified from the transfectant supernates and compared based upon their binding affinity for the TAG72 antigen relative to that of the original cB72.3m4 antibody. The data showed that a single amino acid substitution of tyrosine by phenylalanine and a number of amino acids including serine, asparagine, histidine and arginine at position 97 in the VH CDR3 region all resulted in approximate 18-fold lower binding affinity, whereas the substitution of tyrosine by phenylalanine at position 96 in the VH CDR3 region did not affect the binding affinity of the cB72.3m4 antibody. This suggests that the tyrosine residue at position 97 in the VH CDR3 region is in a contact position in the B72.3/TAG72 antibody/antigen interaction, and that the terminal hydroxyl group of the position 97 tyrosine side-chain contributes hydrogen bonding to the TAG72 antigen, whereas the position 96 tyrosine side-chain does not.","PeriodicalId":79322,"journal":{"name":"Cancer biotherapy","volume":"8 3","pages":"253-62"},"PeriodicalIF":0.0,"publicationDate":"1993-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1089/cbr.1993.8.253","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"18803804","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: 1