Elevated PRAME Expression: What Does this Mean for Treatment of Head and Neck Squamous Cell Carcinoma?

Szczepański, Mirosław J.; Whiteside, Theresa L.

doi:10.2217/bmm.13.68

Cited by 14 publications

(9 citation statements)

References 22 publications

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“…(29) Several authors reported PRAME expression in many cancers, but presently the biological and clinical meaning of this finding is not yet completely elucidated and, in some cases, the association between PRAME expression and disease prognosis is controversial. (30)(31)(32) In particular, in solid malignancies, including head and neck cancer, (33,34) liposarcoma,(35) uveal melanoma, (12,36) osteosarcoma, (37,38) breast cancer (39) and neuroblastoma (40) high PRAME expression correlates with advanced stage disease and poor clinical outcome, whereas in pediatric acute leukemia PRAME overexpression was found to predict good outcome. (41,42) Research.…”

Section: Discussionmentioning

confidence: 99%

Adoptive Immunotherapy Using PRAME-Specific T Cells in Medulloblastoma

et al. 2018

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Medulloblastoma is the most frequent malignant childhood brain tumor with a high morbidity.Identification of new therapeutic targets would be instrumental in improving patient outcomes. We evaluated the expression of the tumor-associated antigen PRAME in biopsies from 60 medulloblastoma patients. PRAME expression was detectable in 82% of tissues independent of molecular and histopathologic subgroups. High PRAME expression also correlated with worse overall survival. We next investigated the relevance of PRAME as a target for immunotherapy. Medulloblastoma cells were targeted using genetically modified T cells with a PRAME-specific TCR (SLL TCR T cells). SLL TCR T cells efficiently killed medulloblastoma HLA-A*02+ DAOY cells as well as primary HLA-A*02+ medulloblastoma cells. Moreover, SLL TCR T cells controlled tumor growth in an orthotopic mouse model of medulloblastoma. To prevent unexpected T cell-related toxicity, an inducible caspase 9 (iC9) gene was introduced in frame with the SLL TCR; this safety switch triggered prompt elimination of genetically-modified T cells. Altogether, these data indicate that T cells genetically modified with a high-affinity, PRAME-specific TCR and iC9 may represent a promising innovative approach for treating HLA-A*02+ medulloblastoma patients.

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Section: Discussionmentioning

confidence: 99%

Adoptive Immunotherapy Using PRAME-Specific T Cells in Medulloblastoma

et al. 2018

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“…For example, to capture melanoma TEX, a combination of mAbs recognizing CSGP4, also known as the high molecular weight melanoma associated antigen (HMWMAg), and GM3 mAb recognizing NeuGc ganglioside can be used for capture of TEX [92,93]. For HNSCC, capture experiments can be performed, e.g., with anti-survivin mAb in combination with PRAME-specific mAb [94,95]. Antibodies to EPCAM have been used to capture TEX in plasma of patients with colon carcinoma [96].…”

Section: Methods For Exosome Isolationmentioning

confidence: 99%

The potential of tumor-derived exosomes for noninvasive cancer monitoring

Whiteside

2015

Expert Review of Molecular Diagnostics

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Tumor-derived exosomes (TEXs) are emerging as a new type of cancer biomarker. TEXs are membrane-bound, virus-size vesicles of endocytic origin present in all body fluids of cancer patients. Based on the expanding albeit incomplete knowledge of their biogenesis, secretion by tumor cells and cancer cell-specific molecular and genetic contents, TEXs are viewed as promising, clinically-relevant surrogates of cancer progression and response to therapy. Preliminary proteomic, genetic and functional profiling of tumor cell-derived or cancer plasma-derived exosomes confirms their unique characteristics. Alterations in protein or nucleic acid profiles of exosomes in plasma of cancer patients responding to therapies appear to correlate with clinical endpoints. However, methods for TEX isolation and separation from the bulk of human plasma-derived exosomes are not yet established and their role as biomarkers remains to be confirmed. Further development and validation of TEXs as noninvasive, liquid equivalents of tumor biopsies are necessary to move this effort forward.

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“…PRAME is a dominant repressor of RAR signaling. Expression of PRAME serves as a poor prognostic marker in many cancers [18][19][20][21] . Consequently, the knockdown of PRAME is expected to be an interesting option for the development of new therapeutic strategies for cancer [22] .…”

Section: Introductionmentioning

confidence: 99%

Impact of Preferentially Expressed Antigen of Melanoma on the Prognosis of Hepatocellular Carcinoma

Oyama

Kanki

Shimizu

et al. 2016

Gastrointest Tumors

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Background:Retinoids, vitamin A and its derivatives, have an antitumor effect on hepatocellular carcinoma (HCC). The function of retinoids is exerted by the complex of retinoic acid (RA) with the heterodimer of retinoid X receptor and the RA receptor. The preferentially expressed antigen of melanoma (PRAME) acts as a dominant repressor of RA signaling by binding to the complex. The significance of PRAME on the prognosis of HCC remains to be clarified. Methods: PRAME mRNA expression was examined by quantitative real-time polymerase chain reaction in both tumor and non-tumor tissues of 100 HCC patients who received surgical resection. The effect of PRAME knockdown on DR5-mediated RA transcriptional activity was examined. Results: In tumor tissues, there were significant associations among PRAME expression, clinical stage, tumor markers, and tumor numbers. In non-tumor tissues, there were significant associations among PRAME expression, overall survival, and disease-free survival. The knockdown of PRAME caused no reduction in DR5-mediated transcriptional activity of RA, suggesting that PRAME acts via other mechanisms than the DR5 RA-responsive elements. Conclusion: Our findings indicate that PRAME expression is a novel prognostic marker in HCC patients.

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Elevated PRAME Expression: What Does this Mean for Treatment of Head and Neck Squamous Cell Carcinoma?

Cited by 14 publications

References 22 publications

Adoptive Immunotherapy Using PRAME-Specific T Cells in Medulloblastoma

Adoptive Immunotherapy Using PRAME-Specific T Cells in Medulloblastoma

The potential of tumor-derived exosomes for noninvasive cancer monitoring

Impact of Preferentially Expressed Antigen of Melanoma on the Prognosis of Hepatocellular Carcinoma

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