{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,4]],"date-time":"2026-10-04T17:45:46Z","timestamp":1791135946902,"version":"4.1.0"},"reference-count":52,"publisher":"American Society of Hematology","issue":"4","content-domain":{"domain":["ashpublications.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2001,2,15]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>There is a growing interest in using antigen-specific T cells for the treatment of human malignancy. For example, adoptive transfer of Epstein-Barr virus (EBV)-specific cytotoxic T lymphocytes (CTLs) has been effective prophylaxis and treatment of EBV-associated lymphoproliferative disease in immunocompromised patients. For all immunotherapies, however, there has been a hypothetical concern that mutations in tumor-specific antigens may lead to tumor escape. We now demonstrate that such events may indeed occur, with lethal outcome. A patient who developed lymphoma after marrow transplantation received donor-derived, EBV-specific CTLs but died with progressive disease. The tumor cells proved substantially less sensitive to cytolysis than the EBV-transformed B-cell line used for CTL generation. The major cytolytic activity of the donor CTL was directed against 2 HLA-A11\u2013restricted epitopes in the viral EBNA-3B antigen. Sequence analysis of this gene in the tumor virus revealed a 245\u2013base pair deletion, which removed these 2 CTL epitopes. Hence, the viral antigen in the tumor had mutated in a way that allowed escape from CTLs. Analysis of EBV polymorphisms demonstrated that before CTL infusion, more than one virus was present, including a virus with wild-type EBNA-3B. After CTL infusion, only the virus with the EBNA-3B deletion could be detected, suggesting that the infused CTLs had selected a resistant strain in vivo. Such an occurrence, even when polyclonal CTL lines are used against genetically stable virus antigens, suggests that escape mutants may be a serious problem when CTL therapy is directed against more unstable tumor cell\u2013derived targets.<\/jats:p>","DOI":"10.1182\/blood.v97.4.835","type":"journal-article","created":{"date-parts":[[2002,7,27]],"date-time":"2002-07-27T12:46:47Z","timestamp":1027774007000},"page":"835-843","update-policy":"https:\/\/doi.org\/10.1182\/blood.2019cm0000","source":"Crossref","is-referenced-by-count":221,"title":["An Epstein-Barr virus deletion mutant associated with fatal lymphoproliferative disease unresponsive to therapy with virus-specific CTLs"],"prefix":"10.1182","volume":"97","author":[{"given":"Stephen","family":"Gottschalk","sequence":"first","affiliation":[{"name":"From the Center for Cell and Gene Therapy, Department of Pediatrics, Baylor College of Medicine, Houston, TX; and St Jude Children's Research Hospital, Memphis, TN."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Catherine Y. C.","family":"Ng","sequence":"additional","affiliation":[{"name":"From the Center for Cell and Gene Therapy, Department of Pediatrics, Baylor College of Medicine, Houston, TX; and St Jude Children's Research Hospital, Memphis, TN."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Margot","family":"Perez","sequence":"additional","affiliation":[{"name":"From the Center for Cell and Gene Therapy, Department of Pediatrics, Baylor College of Medicine, Houston, TX; and St Jude Children's Research Hospital, Memphis, TN."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Colton A.","family":"Smith","sequence":"additional","affiliation":[{"name":"From the Center for Cell and Gene Therapy, Department of Pediatrics, Baylor College of Medicine, Houston, TX; and St Jude Children's Research Hospital, Memphis, TN."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Clare","family":"Sample","sequence":"additional","affiliation":[{"name":"From the Center for 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