Abstract:
:Vaccination with antigens expressed by tumors is one strategy for stimulating enhanced T-cell responses against tumors. However, these peptide vaccines rarely result in efficient expansion of tumor-specific T cells or responses that protect against tumor growth. Mimotopes, or peptide mimics of tumor antigens, elicit increased numbers of T cells that crossreact with the native tumor antigen, resulting in potent antitumor responses. Unfortunately, mimotopes may also elicit cells that do not crossreact or have low affinity for tumor antigen. We previously showed that one such mimotope of the dominant MHC class I tumor antigen of a mouse colon carcinoma cell line stimulates a tumor-specific T-cell clone and elicits antigen-specific cells in vivo, yet protects poorly against tumor growth. We hypothesized that boosting the mimotope vaccine with the native tumor antigen would focus the T-cell response elicited by the mimotope toward high affinity, tumor-specific T cells. We show that priming T cells with the mimotope, followed by a native tumor-antigen boost, improves tumor immunity compared with T cells elicited by the same prime with a mimotope boost. Our data suggest that the improved tumor immunity results from the expansion of mimotope-elicited tumor-specific T cells that have increased avidity for the tumor antigen. The enhanced T cells are phenotypically distinct and enriched for T-cell receptors previously correlated with improved antitumor immunity. These results suggest that incorporation of native antigen into clinical mimotope vaccine regimens may improve the efficacy of antitumor T-cell responses.
journal_name
Cancer Resjournal_title
Cancer researchauthors
Buhrman JD,Jordan KR,U'ren L,Sprague J,Kemmler CB,Slansky JEdoi
10.1158/0008-5472.CAN-12-1005subject
Has Abstractpub_date
2013-01-01 00:00:00pages
74-85issue
1eissn
0008-5472issn
1538-7445pii
0008-5472.CAN-12-1005journal_volume
73pub_type
杂志文章相关文献
CANCER RESEARCH文献大全abstract::We analyzed the gene expression profiles of clinical lung carcinomas using a cDNA microarray containing 27,648 genes or expressed sequence tags, and identified CDCA5 (cell division cycle associated 5) to be upregulated in the majority of lung cancers. Tumor tissue microarray analysis of 262 non-small cell lung cancer ...
journal_title:Cancer research
pub_type: 杂志文章
doi:10.1158/0008-5472.CAN-09-4372
更新日期:2010-07-01 00:00:00
abstract::We evaluated the cytotoxicity of the immunotoxin OKT1-SAP on fresh B-chronic lymphocytic leukemia (B-CLL) cells from 31 consecutive patients. OKT1-SAP comprised the OKT1 (CD5) monoclonal antibody disulfide linked to saporin-6 (SAP) ribosome-inactivating protein from the plant Saponaria officinalis. The effect of OKT1-...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1989-06-15 00:00:00
abstract::Plexiform neurofibromas are benign nerve sheath Schwann cell tumors characterized by biallelic mutations in the neurofibromatosis type 1 (NF1) tumor suppressor gene. Atypical neurofibromas show additional frequent loss of CDKN2A/Ink4a/Arf and may be precursor lesions of aggressive malignant peripheral nerve sheath tum...
journal_title:Cancer research
pub_type: 杂志文章
doi:10.1158/0008-5472.CAN-19-1429
更新日期:2020-11-01 00:00:00
abstract::Mitotic and labeling indices of bone marrow tumor cells were determined from patients with disseminated neuroblastoma. Although pretreatment values were variable, the median indices indicated that only a small proportion of tumor cells were proliferating. The pretreatment indices could not be correlated with presentin...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1977-10-01 00:00:00
abstract::Spontaneous tumors in urodele amphibians have been considered uncommon, and this resistance has sometimes been associated with the natural regenerative capacity of tissues in such species. This report describes spontaneous, nonpigmented, benign epitheliomas which were found in 44 of 1586 (2.8%) adult newts, Cynops pyr...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1979-06-01 00:00:00
abstract::The effect of culture conditions on the glutamylation of methotrexate by intact H35 hepatoma cells and folylpolyglutamate synthetase (FPGS) activity in the corresponding crude extracts has been examined. The rate of cellular glutamylation of methotrexate observed in rapidly dividing cultures was 4-fold higher than con...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1988-05-01 00:00:00
abstract::Cytotoxic T lymphocyte-associated molecule-4 (CTLA-4), a second counterreceptor for the B7 family of costimulatory molecules, functions as a negative regulator of T-cell activation. Here, we investigated whether the blockade of the CTLA-4 function leads to enhancement of antitumor T-cell responses at various stages of...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1997-09-15 00:00:00
abstract::Previous studies have shown that all-trans-retinoic acid fails to inhibit chemically induced transformation in 10T1/2 cells except at toxic levels, whereas retinol and many synthetic retinoids are potent inhibitors. In contrast, in many systems retinoic acid is a more effective modulator of differentiation and carcino...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1987-11-01 00:00:00
abstract::Motility related protein-1 (MRP-1) is a transmembrane glycoprotein that is identical to the CD9 antigen. In previous studies, we showed that various types of cultured tumor cells transfected with MRP-1/CD9 cDNA have low motility and diminished metastatic potential to the lung. More recently we used immunohistochemical...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1995-12-15 00:00:00
abstract::Aberrant methylation of CpG islands acquired in tumor cells in promoter regions is one method for loss of gene function. We determined the frequency of aberrant promoter methylation (referred to as methylation) of the genes retinoic acid receptor beta-2 (RARbeta), tissue inhibitor of metalloproteinase 3 (TIMP-3), p16I...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:2001-01-01 00:00:00
abstract::A case-control study was undertaken to clarify reasons for a four-fold increased incidence of mesothelioma discovered among white males in coastal Tidewater, Va., from 1972 to 1978. Sixty-one cases were identified. Interviews with next of kin revealed that the excess was linked to employment in area shipyards. Three-f...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1980-11-01 00:00:00
abstract::The cultivated mushroom of commerce in the Western hemisphere, Agaricus bisporus, was given p.o. to randomly bred Swiss mice for 3 days and was followed by semisynthetic diet for 4 days each week for life. The mice were 6 weeks old at the beginning of the experiment. As a result of treatment, tumors were induced in th...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1986-08-01 00:00:00
abstract::The purpose of these studies was to determine whether hematogenous clonal pulmonary melanoma metastases originate from the expansion of a single cell and if so, by extrapolation, metastasis can be considered a cloning process. Three different cell lines of murine K-1735 melanoma with different metastatic properties an...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1986-10-01 00:00:00
abstract::Glioblastomas (GBM) are highly infiltrated by myeloid-derived innate immune cells that contribute to the immunosuppressive nature of the brain tumor microenvironment (TME). CD47 has been shown to mediate immune evasion, as the CD47-SIRPα axis prevents phagocytosis of tumor cells by macrophages and other myeloid cells....
journal_title:Cancer research
pub_type: 杂志文章
doi:10.1158/0008-5472.CAN-18-3125
更新日期:2019-05-15 00:00:00
abstract::We report that tumor necrosis factor (TNF) alpha induced a strong antitumor immune reaction when it was produced in arteries leading to tumors by gene transfer in vivo. We used a mouse model carrying a sarcoma-180 tumor in the right footpad and injected the fusogenic liposomes encapsulating the human TNF-alpha gene in...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1998-12-15 00:00:00
abstract::Initially isolated as the dominant suppressor of the mutant epidermal growth factor receptor (ellipse), the Dachshund gene plays a key role in metazoan development regulating the Retinal Determination Gene Network. Herein, the DACH1 gene was expressed in normal prostate epithelial cells with reduced expression in huma...
journal_title:Cancer research
pub_type: 杂志文章
doi:10.1158/0008-5472.CAN-08-3821
更新日期:2009-04-15 00:00:00
abstract::Phosphoinositol-3-kinase (PI3K)/protein kinase B (AKT) and Fms-like tyrosine kinase 3 (FLT3) signaling are aberrantly activated in acute myelogenous leukemia (AML) cells. Constitutively activated AKT and FLT3 regulate leukemia cell survival and resistance to chemotherapy. In this study, we investigated the effects of ...
journal_title:Cancer research
pub_type: 杂志文章
doi:10.1158/0008-5472.CAN-05-1278
更新日期:2006-04-01 00:00:00
abstract::We have developed a model system for assessing the demethylating potential of external agents. Disruption in the DNA methylation pattern was evaluated at the translational level of the Escherichia coli beta-galactosidase coding gene (lacZ). We have constructed a clonal cell line (A4/4 cells) derived from the adenoviru...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1992-10-01 00:00:00
abstract::Recent clinical trials raised concerns regarding the cardiovascular toxicity of selective cyclooxygenase-2 (COX-2) inhibitors and cyclooxygenase-1 (COX-1) is now being reconsidered as a target for chemoprevention. Our aims were to determine whether selective COX-1 inhibition could delay or prevent cancer development a...
journal_title:Cancer research
pub_type: 杂志文章
doi:10.1158/0008-5472.CAN-13-2245
更新日期:2014-01-01 00:00:00
abstract::The retinoblastoma (Rb)-E2F transcriptional regulatory pathway plays a major role in cell-cycle regulation, but its role in invasion and metastasis is less well understood. We find that many genes involved in the invasion of cancer cells, such as matrix metalloproteinases (MMP), have potential E2F-binding sites in the...
journal_title:Cancer research
pub_type: 杂志文章
doi:10.1158/0008-5472.CAN-11-2647
更新日期:2012-01-15 00:00:00
abstract::The mechanisms by which estrogens and antiestrogens modulate breast cancer growth have not been totally defined. We have examined the cell cycle kinetic effects of estrogens and antiestrogens in cultured human breast cancer cell lines. In a previous study, we showed that tamoxifen induces a transition delay in early t...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1984-04-01 00:00:00
abstract::Deregulation of translation initiation factors contributes to many pathogenic conditions, including cancer. Here, we report the definition of a novel regulatory pathway for translational initiation with possible therapeutic import in cancer. Specifically, we found that casein kinase 1ε (CK1ε) is highly expressed in br...
journal_title:Cancer research
pub_type: 杂志文章
doi:10.1158/0008-5472.CAN-13-1175
更新日期:2014-01-01 00:00:00
abstract::The effect of different preparative procedures for electron microscopy on the size and shape of murine oncornaviruses has been studied. With conventional negative staining procedures using neutral sodium phosphotungstate, both murine mammary tumor virus and murine leukemia virus appeared in head-and-tail forms, with a...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1975-03-01 00:00:00
abstract::Human cancer cell lines are commonly used in basic cancer research to understand the behavior of primary tumors. Aberrations in the DNA methylation patterns are nowadays recognized as a hallmark of the cancer cell. However, no comprehensive study defines the DNA methylation environment present in the established cance...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:2003-03-01 00:00:00
abstract::We recently identified the immunoglobulin-CAM CD155/PVR (the poliovirus receptor) as a regulator of cancer invasiveness and glioma migration, but the mechanism through which CD155/PVR controls these processes is unknown. Here, we show that expression of CD155/PVR in rat glioma cells that normally lack this protein enh...
journal_title:Cancer research
pub_type: 杂志文章
doi:10.1158/0008-5472.CAN-05-1890
更新日期:2005-12-01 00:00:00
abstract::Lectin binding [concanavalin A, biotinylated ricinus communis agglutinin, and biotinylated succinylated wheat germ agglutinin (B-SWGA)] was used to detect the glycosylated proteins associated with a residual protein fraction [insoluble in 4% sodium dodecyl sulfate and termed the nuclear residual fraction (NRF)] or wit...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1988-02-01 00:00:00
abstract::Tetrachloro(d,l-trans)-1,2-diaminocyclohexaneplatinum(IV) (tetraplatin) has been considered a prodrug which would be converted rapidly to dichloro(d,l-trans)-1,2-diaminocyclohexaneplatinum(II) [PtCl2(dach)] under physiological conditions. However, the biotransformations of tetraplatin have not been studied in detail. ...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1991-02-01 00:00:00
abstract::Metastatic nonseminomatous testicular germ cell tumors are curable using combination chemotherapy in approximately 80% of patients. In contrast, most other patients with other types of cancer either present with or acquire drug-resistant disease following chemotherapy. Cell lines derived from testis tumors retain hype...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1990-12-01 00:00:00
abstract::Several metabolic processes, such as DNA organization and replication, transcription, and RNA processing are closely associated with the nuclear matrix. Nuclear matrix attachment regions are nucleotide sequences holding DNA tightly complexed with the nuclear scaffold and are resistant to extractions with detergents an...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1993-09-01 00:00:00
abstract::Cancer metastasis is a leading cause of cancer morbidity and mortality. More needs to be learned about mechanisms that control this process. In particular, the role of chemokine receptors in metastasis remains controversial. Here, using a highly metastatic breast cancer (4T1) model, we show that lung metastasis is a f...
journal_title:Cancer research
pub_type: 杂志文章
doi:10.1158/0008-5472.CAN-08-4619
更新日期:2009-07-15 00:00:00