Cancer biotherapy最新文献_第3页

Cancer vaccines: the interferon analogy. 癌症疫苗:干扰素的类比。

Cancer biotherapy Pub Date : 1995-01-01 DOI: 10.1089/cbr.1995.10.1

L E Spitler

引用次数: 2

Reovirus type 3 chemoimmunotherapy of murine lymphoma is abrogated by cyclosporine. 呼肠孤病毒3型化学免疫治疗小鼠淋巴瘤被环孢素废除。

Cancer biotherapy Pub Date : 1995-01-01 DOI: 10.1089/cbr.1995.10.307

T A Steele, D C Cox

{"title":"Reovirus type 3 chemoimmunotherapy of murine lymphoma is abrogated by cyclosporine.","authors":"T A Steele, D C Cox","doi":"10.1089/cbr.1995.10.307","DOIUrl":"https://doi.org/10.1089/cbr.1995.10.307","url":null,"abstract":"We have previously shown that the combined modalities of reovirus type 3 and the chemotherapeutic agent 1,3-bis (2-chloroethyl)-1-nitrosourea (BCNU) synergize to cause the rejection of various murine tumors. Resistance of surviving animals to challenge with homologous but not heterologous tumor suggested that tumor was eliminated through an immune-mediated mechanism. In this study, we showed that mice undergoing therapy-mediated rejection of tumor were able to reject subsequent weekly challenges with EL-4 but not L1210 tumor cells. The mechanism underlying this therapy was investigated using cyclosporine (CS) to suppress immune responsiveness. A dose-related inhibition of therapy was observed with total inhibition occurring at 30 mg/kg/day. Delayed administration of CS at day 14 or later after tumor administration resulted in little or no inhibitory effect. The resistance of cured mice to EL-4 tumor challenge was not affected by CS, which is consistent with the reduced ability of CS to affect secondary immune responses. In addition, CS did not alter natural killer cell activity in mice receiving the BCNU/reovirus therapy. These results suggest that there is an obligatory immune response produced by the BCNU/reovirus therapy which arises early after the administration of the therapy.","PeriodicalId":79322,"journal":{"name":"Cancer biotherapy","volume":"10 4","pages":"307-15"},"PeriodicalIF":0.0,"publicationDate":"1995-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1089/cbr.1995.10.307","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"19570451","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: 22

In vitro and in vivo production of interleukin-6 induced by muramyl peptides and lipopolysaccharide in normal dogs. 正常犬体外和体内脂多糖诱导白细胞介素-6的产生。

Cancer biotherapy Pub Date : 1995-01-01 DOI: 10.1089/cbr.1995.10.317

F Shi, I D Kurzman, E G MacEwen

{"title":"In vitro and in vivo production of interleukin-6 induced by muramyl peptides and lipopolysaccharide in normal dogs.","authors":"F Shi, I D Kurzman, E G MacEwen","doi":"10.1089/cbr.1995.10.317","DOIUrl":"https://doi.org/10.1089/cbr.1995.10.317","url":null,"abstract":"Interleukin-6 (IL-6) is a multifactorial cytokine produced by many cells including monocytes and macrophages in the immune-stimulated host. We measured IL-6 activity induced by muramyl dipeptide (MDP) and lipopolysaccharide (LPS) in vitro and by liposome-encapsulated muramyl tripeptide-phosphatidylethanolamine (L-MTP-PE) in vivo in normal dogs. Adherent mononuclear cells were cultured with MDP, LPS, or MDP plus LPS for various time periods. After incubation, culture supernatants were collected and assayed for IL-6 activity. Sera from dogs following L-MTP-PE administration were also evaluated for IL-6 activity. IL-6 activity both in supernatants and sera was measured using a 7TD1 bioassay. Significantly elevated IL-6 activity could be measured as early as 2 hours after mononuclear cells were exposed to MDP, LPS, or MDP plus LPS. IL-6 activity induced by LPS was greater than that induced by MDP, and the combination of MDP and LPS induced the greatest increase in IL-6 activity. Serum IL-6 activity was elevated within 3 to 4 hours post L-MTP-PE administration and subsequently declined to pretreatment level at 24 hours post injection. Neutralization of supernatant and serum IL-6 activity was not achieved with goat or rabbit anti-recombinant human IL-6 polyclonal antibody. This study demonstrates that MDP and LPS, alone and in combination, can induce enhanced IL-6 activity of canine adherent mononuclear cells in vitro, and that intravenous injection of L-MTP-PE is capable of eliciting increased IL-6 activity in vivo in normal dogs. These findings suggest that IL-6 may play an important role in the biologic response observed in canine cancer patients treated with L-MTP-PE.","PeriodicalId":79322,"journal":{"name":"Cancer biotherapy","volume":"10 4","pages":"317-25"},"PeriodicalIF":0.0,"publicationDate":"1995-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1089/cbr.1995.10.317","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"19570452","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

Augmentation of specific tumor killing activity by tumor-infiltrating lymphocytes (TIL) in the presence of TNF-SAM2. 肿瘤浸润淋巴细胞(TIL)在TNF-SAM2存在下特异性肿瘤杀伤活性的增强

Cancer biotherapy Pub Date : 1995-01-01 DOI: 10.1089/cbr.1995.10.37

S Goto, Y Suma, K Noguchi, J Kera, S Sakai, G I Soma, S Takeuchi

{"title":"Augmentation of specific tumor killing activity by tumor-infiltrating lymphocytes (TIL) in the presence of TNF-SAM2.","authors":"S Goto, Y Suma, K Noguchi, J Kera, S Sakai, G I Soma, S Takeuchi","doi":"10.1089/cbr.1995.10.37","DOIUrl":"https://doi.org/10.1089/cbr.1995.10.37","url":null,"abstract":"The effect of TNF-SAM2 on cytotoxic activity of tumor-infiltrating lymphocytes (TIL) was investigated. TIL were prepared from 11 human cancer patients. They were propagated by double in vitro stimulation with anti-CD3 monoclonal antibody and interleukin-2, and cultured for 3 weeks. The cytotoxic activity of TIL was tested with standard 4h 51Cr-release assays in the presence or the absence of TNF-SAM2. In the presence of TNF-SAM2 (500U/ml), the mean cytotoxic activity against autologous tumor cells was significantly augmented compared to that in its absence. However, the fact that cytotoxic activity against K562 and Daudi showed no difference whether substance was present or not, indicates that LAK and NK activity were not affected by TNF-SAM2. Direct cytotoxicity by exogenously added TNF-SAM2 to tumor cells was measured in 9 out of 11 cases and this revealed that cytotoxicity solely by TNF-SAM2 was seen in 3 tumors. However, there was no correlation between the augmentation of cytotoxicity by TIL in the presence of TNF-SAM2 and the cytotoxicity shown by TNF-SAM2 alone. These results suggested that TIL therapy combined with administration of exogenous TNF may exert a synergistically stronger therapeutic effect on cancer.","PeriodicalId":79322,"journal":{"name":"Cancer biotherapy","volume":"10 1","pages":"37-44"},"PeriodicalIF":0.0,"publicationDate":"1995-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1089/cbr.1995.10.37","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"18783199","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

Subcutaneous interleukin-2 and alpha-interferon in advanced colorectal carcinoma. A phase II study. 皮下白介素-2和α -干扰素在晚期结直肠癌中的作用。一项II期研究。

Cancer biotherapy Pub Date : 1995-01-01 DOI: 10.1089/cbr.1995.10.5

A L Hjelm, P Ragnhammar, J Fagerberg, I Magnusson, J E Frodin, R Svanstrom, J Shetye, H Mellstedt, J P Wersall

{"title":"Subcutaneous interleukin-2 and alpha-interferon in advanced colorectal carcinoma. A phase II study.","authors":"A L Hjelm, P Ragnhammar, J Fagerberg, I Magnusson, J E Frodin, R Svanstrom, J Shetye, H Mellstedt, J P Wersall","doi":"10.1089/cbr.1995.10.5","DOIUrl":"https://doi.org/10.1089/cbr.1995.10.5","url":null,"abstract":"Subcutaneous administration of low doses of recombinant interleukin-2 (IL-2) and interferon-alpha (IFN-alpha) on an out-patient basis has been reported not to significantly compromise the response frequency compared to intravenous IL-2 in patients with renal cell carcinoma and melanoma. As part of an ongoing program to develop a biotherapeutic concept in patients with colorectal carcinoma (CRC) we studied the clinical effects of such a regimen in 15 patients with metastatic CRC. The daily dose of IL-2 varied between 4.8-14.4 x 10(6) U/m2 and of IFN-alpha between 3-6 x 10(6) U/m2. The cycle length was 6 weeks. The course was repeated every 8 weeks until disease progression. Maximum 4 cycles were administered. Maintenance therapy was given to responding patients once a week every month. No patient showed a major response (CR or PR). Six patients had a stable disease ranging from 3 months to 18 months with a median duration time of 5 months. The median survival of all patients was 13 months. The main adverse reactions were fever, chills, anorexia and shortness of breath. No treatment related deaths occurred. 6/14 patients developed abnormal concentration of serum levels of thyroid hormones. It is concluded that the present treatment schedule using IL-2 and IFN-alpha in advanced CRC seemed not to be of clinical benefit.","PeriodicalId":79322,"journal":{"name":"Cancer biotherapy","volume":"10 1","pages":"5-12"},"PeriodicalIF":0.0,"publicationDate":"1995-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1089/cbr.1995.10.5","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"18783201","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: 3

Biotherapy and Radiopharmaceuticals 生物疗法和放射性药物

Cancer biotherapy Pub Date : 1995-01-01 DOI: 10.1089/CBR.1995.10.251

R. Oldham

引用次数: 2

Liposome-encapsulated muramyl tripeptide phosphatidylethanolamine for the treatment of feline mammary adenocarcinoma--a multicenter randomized double-blind study. 脂质体包封的muramyl三肽磷脂酰乙醇胺治疗猫乳腺腺癌——一项多中心随机双盲研究

Cancer biotherapy Pub Date : 1995-01-01 DOI: 10.1089/cbr.1995.10.125

L E Fox, E G MacEwen, I D Kurzman, R R Dubielzig, S C Helfand, D M Vail, W Kisseberth, C London, B R Madewell, C O Rodriguez

引用次数: 25

Haplotype donor-generated graft-versus-leukemia responses: serendipity revisited. 单倍型供体产生的移植物抗白血病反应:偶然性重新审视。

Cancer biotherapy Pub Date : 1995-01-01 DOI: 10.1089/cbr.1995.10.181

B M Wimer

{"title":"Haplotype donor-generated graft-versus-leukemia responses: serendipity revisited.","authors":"B M Wimer","doi":"10.1089/cbr.1995.10.181","DOIUrl":"https://doi.org/10.1089/cbr.1995.10.181","url":null,"abstract":"This re-evaluation of a pilot study conducted nearly three decades ago (1965-1970), in which serendipity played a central role in favorable responses of hematologic malignancies to the administration of adoptive lymphocytes from both parents, has been motivated by clearer understanding. Temporary remissions marking LAK cell-driven graft-versus-leukemia (GvL) responses were observed in four of seven acute leukemia patients associated with unique self-limited graft-versus-host (GvH) reactions that were NK cell and cytokine related. Retinopathy not previously reported in a GvH setting was a consistent manifestation in these patients. Cure was achieved in an eighth patient with acute lymphoblastic leukemia after she had been given effective chemotherapy, an active role for the adoptive therapy indicated by the occurrence of a week of fever suggesting an abortive GvH reaction. Two of five patients with Hodgkin's disease also experienced favorable responses to parental leukocyte therapy, one exhibiting GvH manifestations almost identical to those seen in the acute leukemia patients when given the adoptive therapy successfully to spur recovery from severe herpes zoster that had interrupted curative radiation therapy. The GvH in the other patient was a more typical one, the key effect being an increase in circulating lymphocytes that may have contributed indirectly to cure with subsequent therapy. These and other attempts to apply GvL responses therapeutically, including those currently in favor, exemplify the shortcomings of partial mitogenic responses to alloactivation, which are dependent on engraftment, limited in scope, excessively toxic, and difficult to control. Treatment with mitogens such as PHA would be a superior alternative because of the abilities of these agents to regulate immune responses by simple modulations of dosage, scheduling, and modes of application.","PeriodicalId":79322,"journal":{"name":"Cancer biotherapy","volume":"10 3","pages":"181-94"},"PeriodicalIF":0.0,"publicationDate":"1995-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1089/cbr.1995.10.181","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"19528386","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: 4

Expansion of mucin-reactive T-helper lymphocytes from patients with colorectal cancer. 结直肠癌患者黏液反应性t辅助淋巴细胞的扩增。

Cancer biotherapy Pub Date : 1995-01-01 DOI: 10.1089/cbr.1995.10.115

J A Kim, E W Martin, C J Morgan, W Aldrich, P L Triozzi

{"title":"Expansion of mucin-reactive T-helper lymphocytes from patients with colorectal cancer.","authors":"J A Kim, E W Martin, C J Morgan, W Aldrich, P L Triozzi","doi":"10.1089/cbr.1995.10.115","DOIUrl":"https://doi.org/10.1089/cbr.1995.10.115","url":null,"abstract":"The ability to identify and expand effector cells with reactivity against tumor-associated antigens (TAA) is critical for effective adoptive cellular therapy. The purpose of this study was to assess lymph node lymphocytes sensitized in vivo to the shed TAA TAG-72 as a potential source of cells for adoptive cellular therapy. Lymph nodes containing microscopic tumor and/or shed TAG-72+ mucin were localized using radiolabeled CC49 monoclonal antibody and a gamma detector at the time of exploratory colorectal surgery. Lymph nodes containing microscopic tumor and shed mucin exhibited approximately 40-fold expansion in short-term (< 21 days) cultures with either IL-2 or IL-1 plus IL-2; the combination of IL-2/anti-CD3 monoclonal antibody (mAb) resulted in significantly higher expansion. Cultures generated with IL-2 alone favored the expansion of CD8+ and CD56+ cells, whereas addition of IL-1 or anti-CD3 mAb to IL-2 promoted outgrowth of CD4+ T-cells. The IL-2/anti-CD3 expanded cells exhibited low levels of cytolytic activity in vitro against autologous and allogeneic colon tumor targets. However, CD4+ cells expanded in IL-2/anti-CD3 retained the ability to proliferate in response to TAG-72 mucin-expressing autologous tumor as well as bovine submaxillary mucin (BSM) a soluble TAG-72+ mucin. In addition, CD4+ cells expressed mRNA for IL-2, IL-4, tumor necrosis factor-beta and IFNg, and retained the ability to secrete IL-2 after expansion. Thus, noncytolytic, cytokine-secreting, mucin-reactive T- cells can be expanded from lymph nodes of patients with colorectal cancer.(ABSTRACT TRUNCATED AT 250 WORDS)","PeriodicalId":79322,"journal":{"name":"Cancer biotherapy","volume":"10 2","pages":"115-23"},"PeriodicalIF":0.0,"publicationDate":"1995-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1089/cbr.1995.10.115","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"18667310","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: 10

Stimulation of reactive oxygen species production and cytotoxicity in human neutrophils in vitro and after oral administration of a polyenzyme preparation. 体外和口服多酶制剂后对人中性粒细胞活性氧产生和细胞毒性的刺激。

Cancer biotherapy Pub Date : 1995-01-01 DOI: 10.1089/cbr.1995.10.147

E Zavadova, L Desser, T Mohr

{"title":"Stimulation of reactive oxygen species production and cytotoxicity in human neutrophils in vitro and after oral administration of a polyenzyme preparation.","authors":"E Zavadova, L Desser, T Mohr","doi":"10.1089/cbr.1995.10.147","DOIUrl":"https://doi.org/10.1089/cbr.1995.10.147","url":null,"abstract":"Polymorphonuclear neutrophils (PMN) can be primed for enhanced release of reactive oxygen species (ROS) by exposure to cytokines and biological response modifiers. ROS are considered to possess tumoricidal activity. The polyenzyme preparation Wobenzym (WE) contains pancreatin, papain, bromelain trypsin and chymotrypsin and is used in adjuvant tumor therapy. We investigated killing of WE-exposed PMN against tumor cells and analyzed WE influence on ROS production in a chemiluminescence assay in PMN in vitro and in vivo. Depending on dose WE stimulates the cytotoxic capacity of PMN in vitro against tumor cells (50 micrograms/ml:p < 0.01). Exposure of PMN to Wobenzym caused a time-dependent significant (p < 0.02) increase in release of ROS. Similarly, oral administration of Wobenzym to healthy volunteers (n = 28) resulted in significant increases (p < 0.01) in ROS production, depending on dose (peak with 20 tablets) and time (peak 4 hours after Wobenzym administration). In contrast, ROS production was not elevated in the PMN of healthy volunteers receiving placebo (n = 8) or no treatment (n = 16). These findings point to an immunomodulatory capacity of WE in adjuvant tumor therapy.","PeriodicalId":79322,"journal":{"name":"Cancer biotherapy","volume":"10 2","pages":"147-52"},"PeriodicalIF":0.0,"publicationDate":"1995-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1089/cbr.1995.10.147","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"18667881","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: 31