Characterization of an Antigen That Is Recognized on a Melanoma Showing Partial HLA Loss by CTL Expressing an NK Inhibitory Receptor

Ikeda, Hideyuki; Bernard, Loris; Lehmann, Frédéric; Baren, Nicolas van; Baurain, J.; Smet, Charles De; Chambost, Hérvè; Vitale, Massimo; Moretta, Alessandro; Boon, Thierry; Coulie, Pierre G.

doi:10.1016/s1074-7613(00)80426-4

Cited by 664 publications

(565 citation statements)

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“…PRAME, which was first described in 1997 by Ikeda et al [36], has previously been shown to be expressed in 35-64% of AML patients [29,30,[37][38][39]. On the other hand, we have shown here that PRAME is absent from non-malignant hematopoetic cells, which is in line with our previous analysis of a panel of 23 healthy tissues including PBMC, BM samples, and CD341 progenitor cells from healthy donors [16].…”

Section: Discussionsupporting

confidence: 92%

“…On the other hand, we have shown here that PRAME is absent from non-malignant hematopoetic cells, which is in line with our previous analysis of a panel of 23 healthy tissues including PBMC, BM samples, and CD341 progenitor cells from healthy donors [16]. We propose that PRAME's expression pattern and ability to elicit significant cellular immune responses in vitro [40] and in vivo [36] make it a prime target for antigen-specific immunotherapies of AML.…”

Section: Discussionsupporting

confidence: 91%

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Cancer‐testis antigen expression and its epigenetic modulation in acute myeloid leukemia

et al. 2011

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Cancer-testis antigens (CTA) represent attractive targets for tumor immunotherapy. However, a broad picture of CTA expression in acute myeloid leukemia (AML) is missing. CTA expression was analyzed in normal bone marrow (BM) as well as in AML cell lines before and after treatment with demethylating agents and/or histone acetylase inhibitors. Presence of selected CTA with a strictly tumor-restricted expression was then determined in samples of patients with AML before and after demethylating therapy. Screening AML cell lines for the expression of 20 CTA, we identified six genes (MAGE-A3, PRAME, ROPN1, SCP-1, SLLP1, and SPO11) with an AML-restricted expression. Analyzing the expression of these CTA in blast-containing samples from AML patients (N 5 64), we found all samples to be negative for MAGE-A3 and SPO11 while a minority of patients expressed ROPN1 (1.6%), SCP-1 (3.1%), or SLLP1 (9.4%). The only CTA expressed in substantial proportion of patients (53.1%) was PRAME. Following demethylating treatment with 5 0 -aza-2 0 -deoxycytidine, we observed an increased or de novo expression of CTA, in particular of SSX-2, in AML cell lines. In AML patients, we detected increased expression of PRAME and induction of SSX-2 after demethylating therapy with 5-azacytidine. With the exception of PRAME, CTA are mostly absent from AML blasts. However, demethylating treatment induces strong expression of CTA, particularly of SSX-2, in vitro and in vivo. Therefore, we propose that CTA-specific immunotherapy for AML should preferentially target PRAME and/or should be combined with the application of demethylating agents opening the perspective for alternative targets like CTA SSX-2. Am. J. Hematol. 86:918-922, 2011. V

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Section: Discussionsupporting

confidence: 92%

Section: Discussionsupporting

confidence: 91%

Cancer‐testis antigen expression and its epigenetic modulation in acute myeloid leukemia

et al. 2011

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“…The gene was expressed ubiquitously in normal human tissues at a low level and highly expressed in testis. PRAME was also expressed in many neoplastic tumors including melanoma, lung cancer, renal cancer, and acute leukemia [9]. In the present study, we showed that HOIMS-1 was a PRAME gene and a candidate BCR/ABL-inducible gene.…”

Section: Discussionsupporting

confidence: 57%

“…Whether CTL activity against PRAME-positive leukemic cells is higher in AML patients with AML-1/ETO than CML patients with BCR/ABL requires further investigation. As mentioned above, PRAME mRNA expression was not restricted to leukemia, but distributed to various types of malignant tumors [9]. Hence development of CTL which recognizes PRAME could be useful and applicable for the treatment of various neoplasms as well as leukemia.…”

Section: Discussionmentioning

confidence: 90%

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Identification of a melanoma antigen, PRAME, as a BCR/ABL‐inducible gene

et al. 2000

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In order to elucidate molecular events in BCR/ABLinduced transformation, we adopted a polymerase chain reaction (PCR)-based technique of differential display and compared mRNA expression in human factor-dependent cells, TF-1, with that in factor-independent cells, ID-1, which were established from TF-1 cells by transfection of BCR/ABL. Cloning and sequencing of a gene which was upregulated in ID-1 cells revealed that the gene was identical to a melanoma antigen, PRAME. Our present study demonstrated that PRAME was markedly expressed in primary leukemic cells with chronic myeloid leukemia (CML) in blastic crisis and Philadelphia (Ph) + -acute lymphoblastic leukemia (ALL), in which BCR/ABL played an important role as a pathogenic gene. Moreover, comparison of PRAME expression among CD34 + cells with CML in blastic, accelerated, and chronic phases revealed a higher expression in CML in advanced phases. Thus PRAME was considered to be a good candidate for a marker of Ph + -leukemic blast cells as well as a new target antigen of leukemic blast cells that cytotoxic T cells can recognize.z 2000 Federation of European Biochemical Societies.

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PRAME as a Potential Target for Immunotherapy in Metastatic Uveal Melanoma

et al. 2017

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IMPORTANCE Uveal melanoma (UM) is an intraocular primary malignant neoplasm that often gives rise to metastatic disease for which there are no effective therapies. A substantial proportion of UMs express the cancer-testis antigen PRAME (preferentially expressed antigen in melanoma), which can potentially be targeted by adoptive T-cell therapy.OBJECTIVE To determine whether there may be a rationale for PRAME-directed T-cell therapy for metastatic UM.DESIGN, SETTING, AND PARTICIPANTS An experimental study using a retrospective cohort of 64 patients with UM (median follow-up, 62 months) was conducted from January 8, 2015, to November 20, 2016, at the Leiden University Medical Center. Clinical, histopathologic, and genetic parameters were compared between 64 PRAME-positive and PRAME-negative UMs. HLA class I restricted, PRAME-specific T cells were stimulated with UM cell lines to measure their antigen-specific reactivity against these cell lines, which were analyzed for PRAME expression by real-time quantitative polymerase chain reaction. Uveal melanoma metastases from 16 unrelated patients were assessed for PRAME expression by messenger RNA fluorescence in situ hybridization and for HLA class I expression by immunofluorescence staining.MAIN OUTCOMES AND MEASURES Interferon γ production for antigen-specific reactivity and detection of PRAME and HLA class I expression in primary and metastatic UM. RESULTSOf the 64 patients in the study (31 women and 33 men; mean [SD] age at the time of enucleation, 60.6 [15.6] years), PRAME expression was negative in 35 primary UMs and positive in 29 primary UMs. Positive PRAME expression was associated with a high largest basal diameter (15.0 vs 12.0 mm; P = .005), ciliary body involvement (59% vs 26%; P = .008), and amplification of chromosome 8q (66% vs 23%; P = .002). PRAME-specific T cells reacted against 4 of 7 UM cell lines, demonstrating that T-cell reactivity correlated with PRAME expression. Metastatic UM samples were positive for PRAME messenger RNA in 11 of 16 patients and for HLA class I in 10 of 16 patients, with 8 of 16 patients demonstrating coexpression of both PRAME and HLA class I.CONCLUSIONS AND RELEVANCE PRAME is expressed in many primary and metastatic UMs, and about half of the metastatic UMs coexpress PRAME and HLA class I. The finding that PRAME-specific T cells in this study reacted against PRAME-positive UM cell lines suggests a potential role for PRAME-directed immunotherapy for selected patients with metastatic UM.

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Characterization of an Antigen That Is Recognized on a Melanoma Showing Partial HLA Loss by CTL Expressing an NK Inhibitory Receptor

Cited by 664 publications

References 54 publications

Cancer‐testis antigen expression and its epigenetic modulation in acute myeloid leukemia

Cancer‐testis antigen expression and its epigenetic modulation in acute myeloid leukemia

Identification of a melanoma antigen, PRAME, as a BCR/ABL‐inducible gene

PRAME as a Potential Target for Immunotherapy in Metastatic Uveal Melanoma

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