2. Academic Validation
  3. Closely related T-memory stem cells correlate with in vivo expansion of CAR.CD19-T cells and are preserved by IL-7 and IL-15

Closely related T-memory stem cells correlate with in vivo expansion of CAR.CD19-T cells and are preserved by IL-7 and IL-15

  • Blood. 2014 Jun 12;123(24):3750-9. doi: 10.1182/blood-2014-01-552174.
Yang Xu 1,  Ming Zhang 2,  Carlos A Ramos 3,  April Durett 2,  Enli Liu 2,  Olga Dakhova 2,  Hao Liu 4,  Chad J Creighton 4,  Adrian P Gee 5,  Helen E Heslop 6,  Cliona M Rooney 7,  Barbara Savoldo 8,  Gianpietro Dotti 9
Affiliations

Affiliations

  • 1 Center for Cell and Gene Therapy, Department of Pathology and Immunology, Baylor College of Medicine, Houston, TX;
  • 2 Center for Cell and Gene Therapy.
  • 3 Center for Cell and Gene Therapy, Houston Methodist Hospital, Houston, TX; Department of Medicine, Baylor College of Medicine, Houston, TX;
  • 4 Dan L. Duncan Cancer Center, Division of Biostatistics, Baylor College of Medicine, Houston, TX;
  • 5 Center for Cell and Gene Therapy, Department of Pediatrics, Baylor College of Medicine, Houston, TX; and.
  • 6 Center for Cell and Gene Therapy, Houston Methodist Hospital, Houston, TX; Department of Medicine, Baylor College of Medicine, Houston, TX; Department of Pediatrics, Baylor College of Medicine, Houston, TX; and Texas Children's Hospital, Houston, TX.
  • 7 Center for Cell and Gene Therapy, Department of Pathology and Immunology, Baylor College of Medicine, Houston, TX; Department of Pediatrics, Baylor College of Medicine, Houston, TX; and Texas Children's Hospital, Houston, TX.
  • 8 Center for Cell and Gene Therapy, Department of Pediatrics, Baylor College of Medicine, Houston, TX; and Texas Children's Hospital, Houston, TX.
  • 9 Center for Cell and Gene Therapy, Department of Pathology and Immunology, Baylor College of Medicine, Houston, TX; Department of Medicine, Baylor College of Medicine, Houston, TX; Texas Children's Hospital, Houston, TX.
PMID: 24782509 DOI: 10.1182/blood-2014-01-552174
Abstract

Adoptive transfer of T lymphocytes expressing a CD19-specific chimeric antigen receptor (CAR.CD19) induces complete tumor regression in patients with lymphoid malignancies. Although in vivo persistence of CAR-T cells correlates with clinical responses, it remains unknown whether specific cell subsets within the CAR-T-cell product correlate with their subsequent in vivo expansion and persistence. We analyzed 14 patients with B-cell malignancies infused with autologous CAR.CD19-redirected T cells expanded ex vivo using IL-2, and found that their in vivo expansion only correlated with the frequency within the infused product of a CD8(+)CD45RA(+)CCR7(+) subset, whose phenotype is closest to "T-memory stem cells." Preclinical models showed that increasing the frequency of CD8(+)CD45RA(+)CCR7(+) CAR-T cells in the infused line by culturing the cells with IL-7 and IL-15 produced greater antitumor activity of CAR-T cells mediated by increased resistance to cell death, following repetitive encounters with the antigen, while preserving their migration to secondary lymphoid organs. This trial was registered at www.clinicaltrials.gov as #NCT00586391 and #NCT00709033.

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