Abstract:
:Interleukin (IL)-2 has been approved for treatment of metastatic renal cancer and malignant melanoma. However, its unfavorable pharmacologic properties, severe side effects and the negative role of IL-2 in maintaining T regulatory cells are severe drawbacks. It has been shown that immunocomplexes of IL-2 and certain anti-IL-2 mAbs possess selective and high stimulatory activity in vivo. Here, we show that IL-2/S4B6 mAb immunocomplexes expand not only CD122(high) subsets and newly activated CD8(+) T cells but also natural killer T cells and γδ T cells. Further, we demonstrate that natural killer (NK) cells expanded by IL-2/S4B6 mAb immunocomplexes in vivo have high cytolytic activity, which can be further increased by coadministration of IL-12. We also demonstrate that IL-2/S4B6 mAb immunocomplexes possess noticeable antitumor activity in two syngeneic mouse tumor models, namely BCL1 leukemia and B16F10 melanoma, but only if administered early in tumor progression. To effectively treat established tumors, we administered the tumor-bearing mice first with N-(2-hydroxypropyl)methacrylamide copolymer-bound doxorubicin conjugate, and subsequently with IL-2/S4B6 mAb immunocomplexes alone or with IL-12 to induce an efficient antitumor immune response. Importantly, we show that the conjugate has significantly lower immunosuppressive activity than free doxorubicin when using dosage with comparable antitumor activity, thus eliminating the majority of tumor cells while leaving the immune system mostly unimpaired for stimulation with IL-2/S4B6 mAb immunocomplexes. Indeed, we demonstrate that the conjugate and IL-2/S4B6 mAb immunocomplexes together have synergistic antitumor activity.
journal_name
Int J Cancerjournal_title
International journal of cancerauthors
Tomala J,Chmelova H,Strohalm J,Ulbrich K,Sirova M,Rihova B,Kovar Mdoi
10.1002/ijc.25859subject
Has Abstractpub_date
2011-10-15 00:00:00pages
2002-12issue
8eissn
0020-7136issn
1097-0215journal_volume
129pub_type
杂志文章abstract::Heat shock protein 90 (Hsp90) is a molecular chaperone that promotes the conformational maturation of numerous client proteins, many of which play critical roles in tumor cell growth and survival. The ansamycin-based Hsp90 inhibitor 17-allylamino-17-demethoxygeldanamycin (17-AAG) is currently in Phase III clinical tes...
journal_title:International journal of cancer
pub_type: 杂志文章
doi:10.1002/ijc.24815
更新日期:2010-03-01 00:00:00
abstract::The survival experience of 284 patients with cancer of the cervix uteri registered by the population-based Zimbabwe National Cancer Registry in 1995-1997 is described. The vital status of these subjects was established by linkage with death registration and by retrieval of patient files from medical records department...
journal_title:International journal of cancer
pub_type: 杂志文章
doi:10.1002/ijc.11670
更新日期:2004-03-20 00:00:00
abstract::Melanoma-associated germline mutations affecting the tumor suppressor and cyclin-dependent kinase (CDK) inhibitor, CDKN2A/p16INK4a, have been identified in over 100 melanoma-prone families worldwide. To predict the melanoma risk for carriers of specific mutations, mutant p16INK4a can be tested in biochemical and cellu...
journal_title:International journal of cancer
pub_type: 杂志文章
doi:10.1002/ijc.21265
更新日期:2005-11-20 00:00:00
abstract::Oncogenes of the myc family c-raf-1 and K-ras have been reported to modulate radiosensitivity. We examined the possible relationship between in vivo radiosensitivity to single-dose irradiation with 3-10 Gy, and activity of these proto-oncogenes in 2 sets of small-cell lung cancer (SCLC) xenografts, the CPH and the GLC...
journal_title:International journal of cancer
pub_type: 杂志文章
doi:10.1002/ijc.2910490223
更新日期:1991-09-09 00:00:00
abstract::In order to establish the role of human papillomavirus (HPV) in carcinogenesis of epidermodysplasia verruciformis (EV), the presence, the molecular characteristics and the physical state of HPV DNA in a benign lesion, a primary carcinoma and a metastatic carcinoma developing in the same EV patient were studied and com...
journal_title:International journal of cancer
pub_type: 杂志文章
doi:10.1002/ijc.2910430611
更新日期:1989-06-15 00:00:00
abstract::In order to analyze the mutational events and to understand the biological significance of the p53 gene in chemical carcinogenesis, we applied a new yeast-based p53 functional assay to ovarian tumors induced by 7, 12-dimethylbenz[a]anthracene (DMBA), as well as to transitional cell carcinomas of the urinary bladder in...
journal_title:International journal of cancer
pub_type: 杂志文章
doi:10.1002/(sici)1097-0215(19991126)83:5<700::aid-ijc
更新日期:1999-11-26 00:00:00
abstract::High circulating glucose, insulin resistance and obesity appear to be associated with increased risk of breast cancer (BC). We sought further insight into the relation of these variables to BC. We assessed associations of BC risk with serum fasting glucose, insulin, homeostasis model assessment-insulin resistance (HOM...
journal_title:International journal of cancer
pub_type: 杂志文章
doi:10.1002/ijc.26071
更新日期:2012-02-15 00:00:00
abstract::Laser microdissection (LMD) and microarray were used to identify genes associated with colorectal cancer. Stanniocalcin 2 (STC2) expression and clinicopathological significance in 139 clinical colorectal cancer samples were specifically investigated using real-time quantitative reverse transcription-polymerase chain r...
journal_title:International journal of cancer
pub_type: 杂志文章
doi:10.1002/ijc.24453
更新日期:2009-08-15 00:00:00
abstract::Cancer-germline genes (CGGs) code for immunogenic antigens that are present on various human tumors but not on normal tissues. The importance of CGGs in cancer immunotherapy has led to detailed studies of their expression in a range of human tumors. We measured the levels of expression of 12 CGGs in various pediatric ...
journal_title:International journal of cancer
pub_type: 杂志文章
doi:10.1002/ijc.22118
更新日期:2007-01-01 00:00:00
abstract::Leukocyte functions (superoxide production and phagocytosis) were evaluated in patients with testicular cancer who had undergone super-high-dose chemotherapy (SHDT) with peripheral blood stem cell transplantation (PBSCT). In 5 patients with advanced or relapsed testicular cancer who received 8 cycles of SHDT with PBSC...
journal_title:International journal of cancer
pub_type: 杂志文章
doi:10.1002/(sici)1097-0215(19970703)72:1<39::aid-ijc5
更新日期:1997-07-03 00:00:00
abstract::We have previously reported that the negative signaling regulator Similar Expression to FGF (hSef) is downregulated in prostate cancer and its loss is associated with clinical metastasis. Here, we explored the mechanistic basis of this finding. We first confirmed our clinical observation by testing hSef manipulation i...
journal_title:International journal of cancer
pub_type: 杂志文章
doi:10.1002/ijc.30604
更新日期:2017-04-15 00:00:00
abstract::Progress in the systemic control of osteosarcoma has been limited over the past decades thus indicating the urgent clinical need for the development of novel treatment strategies. Therefore, we have recently developed new preclinical models to study promising novel agents for the treatment of pediatric osteosarcoma. T...
journal_title:International journal of cancer
pub_type: 杂志文章
doi:10.1002/ijc.32814
更新日期:2020-08-15 00:00:00
abstract::The majority of lung cancer patients have tumor-derived genetic alterations in circulating plasma DNA that could be exploited as a diagnostic tool. We used fluorescent microsatellite analysis to detect alterations in plasma and tumor DNA in 34 patients who underwent bronchoscopy for lung cancer, including 11 small cel...
journal_title:International journal of cancer
pub_type: 杂志文章
doi:10.1002/ijc.11079
更新日期:2003-06-20 00:00:00
abstract::Lifestyle factors and medical history are known to influence risk of non-Hodgkin lymphoma (NHL). Whether these factors affect the prognosis of NHL, especially its subtypes, is unclear. To investigate this, the association between these factors and all-cause and lymphoma-related mortality was assessed in a population-b...
journal_title:International journal of cancer
pub_type: 杂志文章
doi:10.1002/ijc.27944
更新日期:2013-06-01 00:00:00
abstract::Established cell lines derived from human malignant astrocytomas typically express a combination of platelet-derived growth factor (PDGF) and PDGF receptor which could form an autocrine loop. In this study, we screened for the essential components of a PDGF autocrine loop in fresh surgical isolates of human astrocytom...
journal_title:International journal of cancer
pub_type: 杂志文章
doi:10.1002/ijc.2910600206
更新日期:1995-01-17 00:00:00
abstract::Retinoic acid (RA) and its natural and synthetic analogs, the retinoids, regulate many biological processes, including development, differentiation, cell growth, morphogenesis, metabolism and homeostasis. Retinoid effects are mediated by specific nuclear receptors, the RARs and RXRs. Because of their ability to contro...
journal_title:International journal of cancer
pub_type: 杂志文章
doi:10.1002/(sici)1097-0215(19990118)80:2<272::aid-ijc
更新日期:1999-01-18 00:00:00
abstract::Posttransplant lymphoproliferative disorder (PTLD) is a common and life-threatening complication of immunosuppression used to prevent rejection of solid organ and bone marrow transplants. There is no standardized treatment algorithm, but numerous management strategies are available. We describe a patient who developed...
journal_title:International journal of cancer
pub_type: 杂志文章
doi:10.1002/(sici)1097-0215(20000420)90:2<104::aid-ijc
更新日期:2000-04-20 00:00:00
abstract::Metaphase comparative genomic hybridisation (CGH) studies indicate that chromosomes 4, 5, 6, 13, 14, 15 and 18 are frequently deleted in primary ovarian cancers (OCs). Therefore we used microcell-mediated chromosome transfer (MMCT) to establish the functional effects of transferring normal copies of these chromosomes ...
journal_title:International journal of cancer
pub_type: 杂志文章
doi:10.1002/ijc.24058
更新日期:2009-03-01 00:00:00
abstract::CD44 is a transmembrane glycoprotein that binds hyaluronan, extracellular matrix proteins and growth factors. Multiple isoforms of CD44 are generated by alternative splicing of 10 separate exons (V1-V10). Expression of the variable exons has been correlated with tumour progression and metastasis in a range of cell typ...
journal_title:International journal of cancer
pub_type: 杂志文章
doi:10.1002/(SICI)1097-0215(19960516)66:4<457::AID-IJC
更新日期:1996-05-16 00:00:00
abstract::Glioma invasion into the surrounding brain tissue is still a major obstacle for any therapeutical approach. As in other solid tumors, matrix-metalloproteases (MMPs) have been suggested as being involved. The aim of this study was to evaluate whether the use of MMP inhibitors to target the protease-mediated invasion pr...
journal_title:International journal of cancer
pub_type: 杂志文章
doi:10.1002/(sici)1097-0215(19990301)80:5<764::aid-ijc
更新日期:1999-03-01 00:00:00
abstract::Actin, a highly conserved protein comprising cell stress fibers and other cellular structures, is found in both the cytoplasm and nucleus of cells and responds to both epigenetic signals and altered gene expression occurring during tumorigenesis. We have previously shown that changes in the cytoplasmic F- and G-actin ...
journal_title:International journal of cancer
pub_type: 杂志文章
doi:10.1002/(sici)1097-0215(19970207)70:4<423::aid-ijc
更新日期:1997-02-07 00:00:00
abstract::Apurinic/apyrimidinic (AP) sites are common mutagenic and cytotoxic DNA lesions that arise from the loss of normal bases. APE1, the major AP endonuclease of human cells, plays a central role in the repair of AP sites through both its endonuclease and phosphodiesterase activities. A common APE1 polymorphism, a T-->G tr...
journal_title:International journal of cancer
pub_type: 杂志文章,多中心研究
doi:10.1002/ijc.21768
更新日期:2006-06-15 00:00:00
abstract::The flavonoids, a group of more than 4,000 polyphenolic antioxidants, are potential cancer preventive components of fruits and vegetables. Catechins, one of the 6 major groups of flavonoids, are present in high concentrations in tea as well. Our objective was to evaluate the association between intake of catechins and...
journal_title:International journal of cancer
pub_type: 杂志文章
doi:10.1002/1097-0215(200102)9999:9999<::aid-ijc1187>3
更新日期:2001-04-15 00:00:00
abstract::Hepatocellular carcinoma (HCC) is the most common type of primary tumor in the liver and is a leading cause of cancer-related death worldwide. Activated hepatic stellate cells (HSCs) are key components of the HCC microenvironment and play an important role in the onset and progression of HCC through the secretion of g...
journal_title:International journal of cancer
pub_type: 杂志文章,评审
doi:10.1002/ijc.32899
更新日期:2020-09-15 00:00:00
abstract::A group of 83 Spanish BC/OC families were analysed for BRCA1 germ-line mutations. Analysis of the entire coding sequence was carried out by SSCP and PTT. We identified 5 frameshift mutations: 185delAG (2 times), 189insTGTC, 1241delAC, and 5537delA and 3 missense mutations in BRCA1: 330A > G, 1240C > T, and 5263G > A. ...
journal_title:International journal of cancer
pub_type: 杂志文章
doi:10.1002/(sici)1097-0215(19991112)83:4<465::aid-ijc
更新日期:1999-11-12 00:00:00
abstract::Results of epidemiologic studies of physical activity and ovarian cancer risk are inconsistent. Few have attempted to measure physical activity over the lifetime or in specific age windows, which may better capture etiologically relevant exposures. We examined participation in moderate-to-vigorous recreational physica...
journal_title:International journal of cancer
pub_type: 杂志文章
doi:10.1002/ijc.32513
更新日期:2020-04-01 00:00:00
abstract::Hepatocellular carcinoma (HCC) is one of the most common cancers worldwide. Little is known about its molecular pathogenesis and the relevance of DNA methylation for disease initiation and progression. Nevertheless, promoter methylation of some genes has been implicated as potential marker for HCC. Thirty-four HCC, 34...
journal_title:International journal of cancer
pub_type: 杂志文章
doi:10.1002/ijc.23433
更新日期:2008-06-15 00:00:00
abstract::We studied the effect of retinoids on the growth and differentiation of a cell line (U 343 MG-A) derived from a human malignant astrocytoma. Cultures treated with all-trans or 13-cis retinoic acid showed a dose-dependent inhibition of proliferation and a marked reduction in the mean cell number at the plateau phase of...
journal_title:International journal of cancer
pub_type: 杂志文章
doi:10.1002/ijc.2910420319
更新日期:1988-09-15 00:00:00
abstract::PAX3 encodes a transcription factor, which with Zic1 is necessary for induction of the neural crest during early embryonic development. There are 7 human PAX3 isoforms (a-h). PAX3e is the full length isoform comprising 10 exons. PAX3c comprises 8 exons plus 5 codons of intron 8, while PAX3g has a truncated transactiva...
journal_title:International journal of cancer
pub_type: 杂志文章
doi:10.1002/ijc.22316
更新日期:2007-03-15 00:00:00
abstract::Transfer of the herpes simplex virus type I thymidine kinase (HSV-TK) gene into tumor cells using virus-based vectors in conjunction with ganciclovir (GCV) exposure provides a potential gene therapy strategy for the treatment of cancer. The possibility of using a novel targetable Sindbis virus expression vector contai...
journal_title:International journal of cancer
pub_type: 杂志文章
doi:10.1002/(sici)1097-0215(19990105)80:1<110::aid-ijc
更新日期:1999-01-05 00:00:00