A mutated intron sequence codes for an antigenic peptide recognized by cytolytic T lymphocytes on a human melanoma.

Coulie, Pierre G.; Lehmann, Frédéric; Bernard, Loris; Herman, Jean; Lurquin, Christophe; Andrawiss, Mariam; Boon, Thierry

doi:10.1073/pnas.92.17.7976

Cited by 367 publications

(183 citation statements)

References 31 publications

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“…Nowadays, we know that such Ags are by and large the results of somatic point mutations occurring in many different proteins expressed by tumor cells (17), and therefore, they represent the only true, tumor-specific Ags not expressed by any normal tissue. Other possible but less frequent mechanisms for generation of these Ags, such as alterations in Unit of Immunotherapy of Human Tumors, Istituto Nazionale Tumori Foundation, Milan, Italy RNA splicing, have been reported (18,19). An important additional feature of unique Ags is their potential resistance to immunoselection in cases when the mutated protein is crucial to the oncogenic process and thus indispensable for maintaining the neoplastic state or because functionally involved in fundamental pathways of cell survival.…”

Section: Unique Ags and Their Main Featuresmentioning

confidence: 99%

Unique Human Tumor Antigens: Immunobiology and Use in Clinical Trials

Parmiani

Filippo

Novellino

et al. 2007

The Journal of Immunology

146

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The individual, unique tumor Ags, which characterize each single tumor, were described 50 years ago in rodents but their molecular characterization was limited to few of them and obtained during the last 20 years. Here we summarize the evidence for the existence and the biological role of such Ags in human tumors, although such evidence was provided only during the last 10 years and by a limited number of studies, a fact leading to a misrepresentation of unique Ags in human tumor immunology. This was also due to the increasing knowledge on the shared, self-human tumor Ags, which have been extensively used as cancer vaccines. In this review, we highlight the biological and clinical importance of unique Ags and suggest how they could be used in clinical studies aimed at assessing their immunogenic and clinical potential both in active and adoptive immunotherapy of human tumors.

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Section: Unique Ags and Their Main Featuresmentioning

confidence: 99%

Unique Human Tumor Antigens: Immunobiology and Use in Clinical Trials

Parmiani

Filippo

Novellino

et al. 2007

The Journal of Immunology

146

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“…Gene MUM-3 contains the third antigenic mutation that is found in the melanoma cells of patient LB33; we previously described two other genes, MUM-1 and MUM-2, that also contain a point mutation leading to the expression of a tumor Ag recognized by autologous CTL (12,13). We therefore considered that the antigenicity of these tumor cells, which may have determined the very favorable clinical evolution of the patient, resulted from the presence of an unusually high number of mutations.…”

Section: Multiple Antigenic Mutations In the Lb33 Melanoma Cellsmentioning

confidence: 99%

“…Three of these Ags were identified. Ag B, presented on HLA-B44, is generated by a point mutation in an ubiquitously expressed gene named MUM-1 (melanoma ubiquitously mutated) (13). Ags K and L, presented on HLA-B44 and HLA-C6, respectively, are produced by a single point mutation in another ubiquitously expressed gene, MUM-2 (12).…”

mentioning

confidence: 99%

High Frequency of Autologous Anti-Melanoma CTL Directed Against an Antigen Generated by a Point Mutation in a New Helicase Gene

Baurain¹,

Colau

Baren

et al. 2000

The Journal of Immunology

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We have identified an Ag recognized by autologous CTL on the melanoma cells of a patient who enjoyed an unusually favorable clinical evolution. The antigenic peptide, which is presented by HLA-A28 molecules, is encoded by a mutated sequence in a new gene. This gene, which was named MUM-3, is expressed ubiquitously and shows homology with the RNA helicase gene family. Limiting dilution analysis indicated that at least 0.15% of the blood CD8 T cells were tumor-specific CTL precursors. The MUM-3 Ag was recognized by 90% of these CTL, indicating that it is the dominant target Ag of the tumor-specific CTL response. The high frequency of anti-MUM-3 CTL was confirmed with tetramers of soluble HLA-A28 molecules loaded with the antigenic peptide. MUM-3 tetramers stained 1.2% of blood CD8 cells, a frequency that has never been reported for T cells directed against a strictly tumor-specific Ag. To confirm these results, the CD8 T cells that were clearly labeled with tetramers were restimulated in clonal conditions. About 90% of these cells proliferated, and all the resulting clones proved lytic and MUM-3 specific. By improving the conditions used for the in vitro restimulation of CTL precursors by the tumor cells, the same frequency could be obtained in limiting dilution analysis. These results show that some cancer patients have a high frequency of circulating CTL that are directed against a strictly tumor-specific Ag. These CTL are responsive to restimulation in vitro and are easily detected with tetramers. Such responses may therefore be an achievable goal for therapeutic vaccination with tumor-specific Ags.

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“…The second group of Ags result from mutations and are therefore unique to each patient. Some examples are ␤-catenin (7), CDK-4 (8), and MUM-1 (9). The third group of Ags are widely expressed in a variety of normal tissues but are selectively overexpressed on tumors.…”

mentioning

confidence: 99%

Pre-Existing Immunity to Tyrosinase-Related Protein (TRP)-2, a New TRP-2 Isoform, and the NY-ESO-1 Melanoma Antigen in a Patient with a Dramatic Response to Immunotherapy

Khong

Rosenberg

2002

The Journal of Immunology

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A mutated intron sequence codes for an antigenic peptide recognized by cytolytic T lymphocytes on a human melanoma.

Abstract: We have identified an antigen recognized on a human melanoma by autologous cytolytic T lymphocytes. It

Cited by 367 publications

References 31 publications

Unique Human Tumor Antigens: Immunobiology and Use in Clinical Trials

Unique Human Tumor Antigens: Immunobiology and Use in Clinical Trials

High Frequency of Autologous Anti-Melanoma CTL Directed Against an Antigen Generated by a Point Mutation in a New Helicase Gene

Pre-Existing Immunity to Tyrosinase-Related Protein (TRP)-2, a New TRP-2 Isoform, and the NY-ESO-1 Melanoma Antigen in a Patient with a Dramatic Response to Immunotherapy

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