{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,30]],"date-time":"2026-10-30T03:22:41Z","timestamp":1793330561619,"version":"4.5.0"},"reference-count":38,"publisher":"American Society of Hematology","issue":"6","content-domain":{"domain":["ashpublications.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2002,3,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Oncogenic anaplastic lymphoma kinase (ALK) fusion proteins (NPM\/ALK and associated variants) are expressed in about 60% of anaplastic large cell lymphomas (ALCLs) but are absent in normal tissues. In this study, we investigated whether ALK, which is expressed at high levels in lymphoma cells, could be a target for antigen-specific cell-mediated immunotherapy. A panel of ALK-derived peptides was tested for their binding affinity to HLA-A*0201 molecules. Binding peptides were assessed for their capacity to elicit a specific immune response mediated by cytotoxic T lymphocytes (CTLs) both in vivo, in HLA-A*0201 transgenic mice, and in vitro in the peripheral blood lymphocytes (PBLs) from healthy donors. Two HLA-A*0201\u2013restricted CTL epitopes, p280-89 (SLAMLDLLHV) and p375-86 (GVLLWEIFSL), both located in the ALK kinase domain were identified. The p280-89\u2013 and p375-86\u2013induced peptide-specific CTL lines were able to specifically release interferon-\u03b3 (IFN-\u03b3) on stimulation with ALK peptide-pulsed autologous Epstein-Barr virus\u2013transformed B cells (LCLs) or T2 cells. Anti-ALK CTLs lysed HLA-matched ALCL and neuroblastoma cell lines endogenously expressing ALK proteins. CTL activity was inhibited by anti-HLA-A2 monoclonal antibody CR11.351, consistent with a class I\u2013restricted mechanism of cytotoxicity. These results show the existence of functional anti-ALK CTL precursors within the peripheral T-cell repertoire of healthy donors, clearly indicating ALK as a tumor antigen and ALK-derived peptides, p280-89 and p375-86, as suitable epitopes for the development of vaccination strategies.<\/jats:p>","DOI":"10.1182\/blood.v99.6.2100","type":"journal-article","created":{"date-parts":[[2002,10,1]],"date-time":"2002-10-01T17:48:18Z","timestamp":1033494498000},"page":"2100-2106","update-policy":"https:\/\/doi.org\/10.1182\/blood.2019cm0000","source":"Crossref","is-referenced-by-count":90,"title":["ALK as a novel lymphoma-associated tumor antigen: identification of 2 HLA-A2.1\u2013restricted CD8+ T-cell epitopes"],"prefix":"10.1182","volume":"99","author":[{"given":"Lorena","family":"Passoni","sequence":"first","affiliation":[{"name":"From the Oncogenic Fusion Genes and Proteins Unit, Istituto Nazionale per lo Studio e la Cura dei Tumori, Milan, Italy; INSERM U.487, Institut Gustave Roussy, Villejuif, France; and Unite\u0301 d'Immunite\u0301 Cellulaire Antivirale, Department SIDA-Retrovirus, Institut Pasteur, Paris, France."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonio","family":"Scardino","sequence":"additional","affiliation":[{"name":"From the Oncogenic Fusion Genes and Proteins Unit, Istituto Nazionale per lo Studio e la Cura dei Tumori, Milan, Italy; INSERM U.487, Institut Gustave Roussy, Villejuif, France; and Unite\u0301 d'Immunite\u0301 Cellulaire Antivirale, Department SIDA-Retrovirus, Institut Pasteur, Paris, France."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carla","family":"Bertazzoli","sequence":"additional","affiliation":[{"name":"From the Oncogenic Fusion Genes and Proteins Unit, Istituto Nazionale per lo Studio e la Cura dei Tumori, Milan, Italy; INSERM U.487, Institut Gustave Roussy, Villejuif, France; and Unite\u0301 d'Immunite\u0301 Cellulaire Antivirale, Department SIDA-Retrovirus, Institut Pasteur, Paris, France."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Barbara","family":"Gallo","sequence":"additional","affiliation":[{"name":"From the Oncogenic Fusion Genes and Proteins Unit, Istituto Nazionale per lo Studio e la Cura dei Tumori, Milan, Italy; INSERM U.487, Institut Gustave Roussy, Villejuif, France; and Unite\u0301 d'Immunite\u0301 Cellulaire Antivirale, Department SIDA-Retrovirus, Institut Pasteur, Paris, France."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Addolorata M. L.","family":"Coluccia","sequence":"additional","affiliation":[{"name":"From the Oncogenic Fusion Genes and Proteins Unit, Istituto Nazionale per lo Studio e la Cura dei Tumori, Milan, Italy; INSERM U.487, Institut Gustave Roussy, Villejuif, France; and Unite\u0301 d'Immunite\u0301 Cellulaire Antivirale, Department SIDA-Retrovirus, Institut Pasteur, Paris, France."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Franc\u0327ois A.","family":"Lemonnier","sequence":"additional","affiliation":[{"name":"From the Oncogenic Fusion Genes and Proteins Unit, Istituto Nazionale per lo Studio e la Cura dei Tumori, Milan, Italy; INSERM U.487, Institut Gustave Roussy, Villejuif, France; and Unite\u0301 d'Immunite\u0301 Cellulaire Antivirale, Department SIDA-Retrovirus, Institut Pasteur, Paris, France."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Konstadinos","family":"Kosmatopoulos","sequence":"additional","affiliation":[{"name":"From the Oncogenic Fusion Genes and Proteins Unit, Istituto Nazionale per lo Studio e la Cura dei Tumori, Milan, Italy; INSERM U.487, Institut Gustave Roussy, Villejuif, France; and Unite\u0301 d'Immunite\u0301 Cellulaire Antivirale, Department SIDA-Retrovirus, Institut Pasteur, Paris, France."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carlo","family":"Gambacorti-Passerini","sequence":"additional","affiliation":[{"name":"From the Oncogenic Fusion Genes and Proteins Unit, Istituto Nazionale per lo Studio e la Cura dei Tumori, Milan, Italy; INSERM U.487, Institut Gustave Roussy, Villejuif, France; and Unite\u0301 d'Immunite\u0301 Cellulaire Antivirale, Department SIDA-Retrovirus, Institut Pasteur, Paris, France."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"234","reference":[{"key":"2020021221092392000_B1","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1007\/s002620000169","article-title":"A listing of human tumor antigens recognized by T 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