{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,11]],"date-time":"2026-03-11T23:28:39Z","timestamp":1773271719822,"version":"3.50.1"},"reference-count":45,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2021,5,25]],"date-time":"2021-05-25T00:00:00Z","timestamp":1621900800000},"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. Oncol."],"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>The use of T cells expressing chimeric antigen receptor (CAR T) engineered to target CD19 constitutes breakthrough treatment for relapsed or refractory B cell non-Hodgkin lymphoma (R\/R B-NHL). Despite improved outcomes, high relapse rate remains a challenge to overcome. Here, we report the clinical results and the pharmacokinetics of bispecific CD19\/22 CAR T in patients with R\/R B-NHL.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We performed a prospective, single-arm study of bispecific CD19\/22 CAR T cells in R\/R B-NHL. We analyzed the safety and efficacy and investigated the kinetic profiles of the CAR T cells. CAR transgene levels were measured using quantitative polymerase chain reaction, and correlation analyses of pharmacodynamic markers and\u00a0product characteristics, disease conditions, clinical efficacy and adverse events were performed.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>From August 2017 to September 2020, a total of 32 patients with CD19\/22 CAR T administration were analyzed. The overall response rate was 79.3%, and the complete response rate was 34.5%. The progression-free survival (PFS) and overall survival (OS) rates at 12 months were 40.0% and 63.3%, respectively. Among patients who had a CR at 3 months, the PFS and OS rates at 12 months were 66.7% and 100%, respectively. Severe cytokine release syndrome (sCRS) (grade 3 and higher) occurred in nine patients (28.1%). Grade 3 or higher neurologic events occurred in four patients (12.5%). One patient died from irreversible severe CRS-associated acute kidney injury. Long-term CAR T cells persistence correlated with clinical efficacy (133 days vs 22 days, P = 0.004). Patients treated with more than three prior therapies and presenting extranodal organ involvement had lower maximal concentration (C<jats:sub>max<\/jats:sub>) values than other patients. Responders had higher C<jats:sub>max<\/jats:sub> and area under the curve values than non-responders. Tumour burden and C<jats:sub>max<\/jats:sub> were potentially associated with the severity of CRS.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>This study demonstrates the safety and potential clinical efficacy of bispecific CD19\/22 CAR T cells in patients with R\/R B-NHL and highlights the importance of measuring kinetic parameters in PB to predict efficacy and safety in clinical applications of CAR T cell therapy.<\/jats:p><\/jats:sec><jats:sec><jats:title>Clinical Trial Registration<\/jats:title><jats:p><jats:uri>https:\/\/www.clinicaltrials.gov\/ct2\/show\/NCT03196830<\/jats:uri>, identifier NCT03196830.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fonc.2021.664421","type":"journal-article","created":{"date-parts":[[2021,5,25]],"date-time":"2021-05-25T07:47:32Z","timestamp":1621928852000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":31,"title":["A Prospective Investigation of Bispecific CD19\/22 CAR T Cell Therapy in Patients With Relapsed or Refractory B Cell Non-Hodgkin Lymphoma"],"prefix":"10.3389","volume":"11","author":[{"given":"Ying","family":"Zhang","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jiaqi","family":"Li","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiaoyan","family":"Lou","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiaochen","family":"Chen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhou","family":"Yu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Liqing","family":"Kang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jia","family":"Chen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jin","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiangping","family":"Zong","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhen","family":"Yang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Minghao","family":"Li","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nan","family":"Xu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sixun","family":"Jia","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hongzhi","family":"Geng","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Guanghua","family":"Chen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Haiping","family":"Dai","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiaowen","family":"Tang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lei","family":"Yu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Depei","family":"Wu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Caixia","family":"Li","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2021,5,25]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1634\/theoncologist.2015-0421","article-title":"Chimeric 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