PRAME as an Independent Biomarker for Metastasis in Uveal Melanoma

Field, Matthew G.; Decatur, Christina L.; Kurtenbach, Stefan; Gezgin, Gülçin; Velden, Pieter A. van der; Jager, Martine J.; Kozak, Kaleigh N.; Harbour, J. William

doi:10.1158/1078-0432.ccr-15-2071

Cited by 223 publications

(218 citation statements)

References 34 publications

Supporting

Mentioning

212

Contrasting

Order By: Relevance

“…A low expression of PRAME correlated with a better 5-year OS probability, a finding similar to that observed in other cancers. (33,36,39,40) Moreover, the correlation between better OS and low PRAME expression was detected in patients belonging to SHH-and G3-MB subgroups, while a larger number of patients is needed to confirm this finding in WNT-and G4-MB subgroups. The statistically significant correlation between low PRAME expression and better OS probability was also maintained considering as cut-off for PRAME mRNA expression median value, as well as 1° and 3° quartiles.…”

Section: Discussionmentioning

confidence: 90%

“…(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%

See 1 more Smart Citation

Adoptive Immunotherapy Using PRAME-Specific T Cells in Medulloblastoma

et al. 2018

View full text Add to dashboard Cite

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.

show abstract

Section: Discussionmentioning

confidence: 90%

Section: Discussionmentioning

confidence: 99%

Adoptive Immunotherapy Using PRAME-Specific T Cells in Medulloblastoma

et al. 2018

View full text Add to dashboard Cite

show abstract

“…These findings derived from primary uveal tumors have allowed us to identify a gene expression profile that is highly accurate for identifying patients at increased risk for metastatic disease [45,46]. The development of a clinically practical platform for analyzing gene expression profiles would benefit those patients at high risk for metastatic disease by strengthening surveillance efforts, permitting earlier treatment, and facilitating the enrollment of suitable patients into ongoing clinical trials [45].…”

Section: Pathogenesismentioning

confidence: 99%

Uveal Melanoma: A Review of the Literature

2018

View full text Add to dashboard Cite

Melanomas affecting different components of the uvea occur with differing frequencies and clinical presentations. Uveal melanoma is diagnosed via funduscopic exam and ancillary tests. These lesions may present with visual findings or incidental findings on physical exam. Metastasis occurs in approximately half of all patients with primary uveal melanoma. The liver is the most common site of metastasis. Enucleation was at one time considered the definitive local treatment for primary uveal melanoma, but has been largely replaced by other therapeutic procedures that aim to prevent metastasis while preserving vision. Unfortunately, metastasis of uveal melanoma almost always proves to be fatal. The current treatment of metastatic uveal melanoma is limited by the intrinsic resistance of uveal melanoma to conventional systemic therapies. Advancements in molecular biology have resulted in the identification of a number of promising prognostic and therapeutic targets. Early detection and therapy are important factors in disease survival. It is imperative that the treating physician be familiar with the clinical features of uveal melanoma and distinguish it from mimickers in order to ensure effective and timely treatment.

show abstract

“…7 NY-ESO-1 is expressed heterogeneously in SS, with only 56% of tumors expressing the antigen in more than 50% of the tumor cells. 11 PRAME-TCR engineered T-cells could be used for the treatment of other cancers as well, including medulloblastoma, since many tumor types express PRAME 8 – 10 , 12 – 14 . PRAME-TCR engineered T-cells are currently used for the treatment of refractory or relapsed acute myeloid leukemia (AML) in a phase I TCR-gene therapy trial (ClinicalTrials.gov NCT02743611).…”

Section: Discussionmentioning

confidence: 99%

PRAME and HLA Class I expression patterns make synovial sarcoma a suitable target for PRAME specific T-cell receptor gene therapy

et al. 2018

View full text Add to dashboard Cite

Synovial sarcoma expresses multiple cancer testis antigens that could potentially be targeted by T-cell receptor (TCR) gene therapy. In this study we investigated whether PRAME-TCR-gene therapy could be an effective treatment for synovial sarcoma by investigating the potential of PRAME-specific T-cells to recognize sarcoma cells and by evaluating the expression patterns of PRAME and HLA class I (HLA-I) in synovial sarcoma tumor samples. All PRAME expressing sarcoma cell lines, including 2 primary synovial sarcoma cell cultures (passage < 3), were efficiently recognized by PRAME-specific T-cells. mRNA FISH demonstrated that PRAME was expressed in all synovial sarcoma samples, mostly in an homogeneous pattern. Immunohistochemistry demonstrated low HLA-I baseline expression in synovial sarcoma, but its expression was elevated in specific areas of the tumors, especially in biphasic components of biphasic synovial sarcoma. In 5/11 biphasic synovial sarcoma patients and in 1/17 monophasic synovial sarcoma patients, elevated HLA-I on tumor cells was correlated with infiltration of T-cells in these specific areas. In conclusion, low-baseline expression of HLA-I in synovial sarcoma is elevated in biphasic areas and in areas with densely infiltrating T-cells, which, in combination with homogeneous and high PRAME expression, makes synovial sarcoma potentially a suitable candidate for PRAME-specific TCR-gene therapy.

show abstract

PRAME as an Independent Biomarker for Metastasis in Uveal Melanoma

Cited by 223 publications

References 34 publications

Adoptive Immunotherapy Using PRAME-Specific T Cells in Medulloblastoma

Adoptive Immunotherapy Using PRAME-Specific T Cells in Medulloblastoma

Uveal Melanoma: A Review of the Literature

PRAME and HLA Class I expression patterns make synovial sarcoma a suitable target for PRAME specific T-cell receptor gene therapy

Contact Info

Product

Resources

About