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A Phase I/IIa Trial...
A Phase I/IIa Trial Using CD19-Targeted Third-Generation CAR T Cells for Lymphoma and Leukemia
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- Enblad, Gunilla (author)
- Uppsala universitet,Experimentell och klinisk onkologi
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- Karlsson, Hannah, 1979- (author)
- Uppsala universitet,Experimentell och klinisk onkologi
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- Gammelgård, Gustav (author)
- Uppsala universitet,Experimentell och klinisk onkologi
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- Wenthe, Jessica (author)
- Uppsala universitet,Klinisk immunologi
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- Lövgren, Tanja (author)
- Uppsala universitet,Klinisk immunologi
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- Amini, Rose-Marie (author)
- Uppsala universitet,Klinisk och experimentell patologi,Rose-Marie Amini
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- Wikstrom, Kristina I. (author)
- Karolinska Univ Hosp Huddinge, VECURA, Stockholm, Sweden
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- Essand, Magnus (author)
- Uppsala universitet,Klinisk immunologi
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- Savoldo, Barbara (author)
- Baylor Coll Med, Ctr Cell & Gene Therapy, Houston, TX 77030 USA
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- Hallböök, Helene (author)
- Uppsala universitet,Hematologi
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- Höglund, Martin (author)
- Uppsala universitet,Hematologi
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- Dotti, Gianpietro (author)
- Baylor Coll Med, Ctr Cell & Gene Therapy, Houston, TX 77030 USA
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- Brenner, Malcolm K. (author)
- Baylor Coll Med, Ctr Cell & Gene Therapy, Houston, TX 77030 USA
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- Hagberg, Hans (author)
- Uppsala universitet,Experimentell och klinisk onkologi
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- Loskog, Angelica, 1973- (author)
- Uppsala universitet,Klinisk immunologi
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(creator_code:org_t)
- 2018
- 2018
- English.
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In: Clinical Cancer Research. - 1078-0432 .- 1557-3265. ; 24:24, s. 6185-6194
- Related links:
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https://urn.kb.se/re...
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https://doi.org/10.1...
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Abstract
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- Purpose: The chimeric antigen receptor (CAR) T-cell therapy has been effective for patients with CD19(+) B-cell malignancies. Most studies have investigated the second-generation CARs with either CD28 or 4-1BB costimulatory domains in the CAR receptor. Here, we describe the first clinical phase I/IIa trial using third-generation CAR T cells targeting CD19 to evaluate safety and efficacy.Patients and Methods: Fifteen patients with B-cell lymphoma or leukemia were treated with CAR T cells. The patients with lymphoma received chemotherapy during CAR manufacture and 11 of 15 were given low-dose cyclophosphamide and fludarabine conditioning prior to CAR infusion. Peripheral blood was sampled before and at multiple time points after CAR infusion to evaluate the persistence of CAR T cells and for immune profiling, using quantitative PCR, flow cytometry, and a proteomic array.Results: Treatment with third-generation CAR T cells was generally safe with 4 patients requiring hospitalization due to adverse reactions. Six of the 15 patients had initial complete responses [4/11 lymphoma and 2/4 acute lymphoblastic leukemia (ALL)], and 3 of the patients with lymphoma were in remission at 3 months. Two patients are still alive. Best predictor of response was a good immune status prior to CAR infusion with high IL12, DC-Lamp, Fas ligand, and TRAIL. Responding patients had low monocytic myeloid-derived suppressor cells (MDSCs; CD14(+)CD33(+)HLA(-)DR(-)) and low levels of IL6, IL8, NAP3, sPDL1, and sPDL2.Conclusions: Third-generation CARs may be efficient in patients with advanced B-cell lymphoproliferative malignancy with only modest toxicity. Immune profiling pre- and posttreatment can be used to find response biomarkers.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Cancer och onkologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Cancer and Oncology (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Hematologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Hematology (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Klinisk laboratoriemedicin (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Clinical Laboratory Medicine (hsv//eng)
Keyword
- Patologi
- Pathology
Publication and Content Type
- ref (subject category)
- art (subject category)
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- By the author/editor
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Enblad, Gunilla
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Karlsson, Hannah ...
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Gammelgård, Gust ...
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Wenthe, Jessica
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Lövgren, Tanja
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Amini, Rose-Mari ...
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Wikstrom, Kristi ...
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Essand, Magnus
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Savoldo, Barbara
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Hallböök, Helene
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Höglund, Martin
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Dotti, Gianpietr ...
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Brenner, Malcolm ...
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Hagberg, Hans
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Loskog, Angelica ...
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- About the subject
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Clinical Medicin ...
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and Cancer and Oncol ...
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Clinical Medicin ...
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and Hematology
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Clinical Medicin ...
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and Clinical Laborat ...
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Clinical Cancer ...
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Uppsala University