{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,20]],"date-time":"2026-10-20T19:57:21Z","timestamp":1792526241447,"version":"4.5.0"},"reference-count":30,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2023,2,8]],"date-time":"2023-02-08T00:00:00Z","timestamp":1675814400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Med."],"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>Immunocompromised patients are susceptible to high-risk opportunistic infections and malignant diseases. Most antiviral and antifungal drugs are quite toxic, relatively ineffective, and induce resistance in the long term. The transfer of pathogen-specific Cytotoxic T-Lymphocytes has shown a minimal toxicity profile and effectiveness in treating Cytomegalovirus, Adenovirus, Epstein - Barr virus, BK Virus and <jats:italic>Aspergillus<\/jats:italic> infections, but this therapy have the main limitations of regulatory issues, high cost, and absence of public cell banks. However, CD45RA<jats:sup>\u2013<\/jats:sup> cells containing pathogen-specific memory T-cells involve a less complex manufacturing and regulatory process and are cheaper, feasible, safe, and potentially effective.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We present preliminary data from six immunocompromised patients: four who had severe infectious diseases and two who had EBV lymphoproliferative disease. All of them underwent multiple safe familial CD45RA<jats:sup>\u2013<\/jats:sup> T-cell infusions as adoptive passive cell therapy, containing Cytomegalovirus, Epstein - Barr virus, BK virus, and <jats:italic>Aspergillus<\/jats:italic>-specific memory T-cells. We also present the method for selecting the best donors for CD45RA<jats:sup>\u2013<\/jats:sup> cells in each case and the procedure to isolate and store these cells.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The infusions were safe, there was no case of graft-versus host disease, and they showed a clear clinical benefit. The patients treated for BK virus nephritis, Cytomegalovirus encephalitis, Cytomegalovirus reactivation, and disseminated invasive aspergillosis experienced pathogen clearance, complete resolution of symptoms in 4-6 weeks and a lymphocyte increase in 3 of 4 cases after 3\u20134 months. Donor T cell transient microchimerism was detected in one patient. The two patients treated for EBV lymphoproliferative disease underwent chemotherapy and several infusions of CD45RA<jats:sup>\u2013<\/jats:sup> memory T-cells containing EBV cytotoxic lymphocytes. Donor T-cell microchimerism was observed in both patients. The viremia cleared in one of the patients, and in the other, despite the viremia not clearing, hepatic lymphoproliferative disease remained stable and was ultimately cured with EBV-specific Cytotoxic T-Lymphocytes.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>The use of familial CD45RA<jats:sup>\u2013<\/jats:sup> T-cells containing specific Cytotoxic T-lymphocytes is a feasible, safe and potential effective approach for treating severe pathogen infections in immunocompromised patients through a third party donor. Furthermore, this approach might be of universal use with fewer institutional and regulatory barriers.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fmed.2023.1083215","type":"journal-article","created":{"date-parts":[[2023,2,8]],"date-time":"2023-02-08T04:52:52Z","timestamp":1675831972000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":15,"title":["Familial CD45RA\u2013 T cells to treat severe refractory infections in immunocompromised patients"],"prefix":"10.3389","volume":"10","author":[{"given":"Karima","family":"Al-Akioui Sanz","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carlos","family":"Echecopar Parente","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cristina","family":"Ferreras","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marta","family":"Men\u00e9ndez Ribes","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alfonso","family":"Navarro","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carmen","family":"Mestre","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura","family":"Clares","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jos\u00e9 Luis","family":"Vicario","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonio","family":"Balas","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raquel","family":"De Paz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eduardo","family":"L\u00f3pez Granados","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elena","family":"S\u00e1nchez Zapardiel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carlos","family":"Jim\u00e9nez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mar\u00eda","family":"L\u00f3pez-Oliva","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Esther","family":"Ramos","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francisco","family":"Hern\u00e1ndez-Oliveros","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonio","family":"P\u00e9rez-Mart\u00ednez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2023,2,8]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"1328","DOI":"10.1056\/NEJMra032015","article-title":"Persistence of the Epstein\u2013Barr virus and the origins of associated lymphomas.","volume":"350","author":"Thorley-Lawson","year":"2004","journal-title":"N Engl J Med."},{"key":"B2","doi-asserted-by":"publisher","first-page":"83","DOI":"10.1007\/s00430-008-0082-5","article-title":"Dynamics of T cell memory in human cytomegalovirus infection.","volume":"197","author":"Waller","year":"2008","journal-title":"Med Microbiol Immunol."},{"key":"B3","doi-asserted-by":"publisher","first-page":"395","DOI":"10.1007\/s00430-014-0348-z","article-title":"The role of CD4+ T cells in BKV-specific T cell immunity.","volume":"203","author":"Weist","year":"2014","journal-title":"Med Microbiol Immunol."},{"key":"B4","doi-asserted-by":"publisher","first-page":"12","DOI":"10.1111\/imr.12138","article-title":"Antiviral T-cell therapy.","volume":"258","author":"Leen","year":"2014","journal-title":"Immunol Rev."},{"key":"B5","doi-asserted-by":"crossref","DOI":"10.1002\/btm2.10214","article-title":"Cell therapies in the clinic.","volume":"6","author":"Wang","year":"2021","journal-title":"Bioeng Transl Med."},{"key":"B6","doi-asserted-by":"publisher","first-page":"1505","DOI":"10.1111\/trf.16354","article-title":"The role of early natural killer cell adoptive infusion before engraftment in protecting against human herpesvirus-6B encephalitis after na\u00efve T-cell-depleted allogeneic stem cell transplantation.","volume":"61","author":"Gasior","year":"2021","journal-title":"Transfusion."},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1038\/bmt.2014.324","article-title":"Rapid memory T-cell reconstitution recapitulating CD45RA-depleted haploidentical transplant graft content in patients with hematologic malignancies. 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