Effects of starting cellular material composition on chimeric antigen receptor T-cell expansion and characteristics

Nasha Elavia, Sandhya R. Panch, Andrew McManus, Thejaswi Bikkani, James Szymanski, Steven L. Highfill, Ping Jin, Jennifer Brudno, James Kochenderfer, David F. Stroncek

Research output: Contribution to journalArticle

4 Scopus citations

Abstract

BACKGROUND: When manufacturing chimeric antigen receptor (CAR) T cells using anti-CD3/anti-CD28 beads, ex vivo T-cell expansion is dependent on the composition of leukocytes used in the manufacturing process. We investigated the effects of leukocyte composition on CAR T-cell expansion and characteristics using an alternative manufacturing method. METHODS: Anti–B-cell maturation antigen and CD19-CAR T cells were manufactured using autologous peripheral blood mononuclear cell (PBMNC) concentrates. The PBMNCs were enriched for lymphocytes using density gradient separation, which were used for CAR T-cell culture initiation. T-cell expansion was stimulated with soluble anti-CD3 and interleukin-2. RESULTS: Fifty-one CAR T-cell products were evaluated; 28 anti–B-cell maturation antigen (BCMA) CAR T cells produced for 24 patients and 27 CD19 CAR T cells produced for 24 patients. CAR T-cell expansion was reduced when greater quantities of monocytes were present in the post–density gradient separation PBMNCs. In addition, the ratio of CD4 to CD8 cells in the CAR T-cell products after 7 days of culture was dependent on the quantity of monocytes, RBCs, and neutrophils in the post–density gradient separation PBMNCs. Greater quantities of monocytes and RBCs were associated with a greater proportion of CD4+ cells and greater quantities of neutrophils were associated with a greater proportion of CD8+ cells. CONCLUSIONS: The composition of leukocytes used to manufacture CAR T cells can affect cell expansion and the composition of CAR T-cell products. More uniform or complete lymphocyte enrichment of PBMNCs improves the consistency of final CAR T-cell products.

Original languageEnglish (US)
Pages (from-to)1755-1764
Number of pages10
JournalTransfusion
Volume59
Issue number5
DOIs
StatePublished - May 2019
Externally publishedYes

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Hematology

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    Elavia, N., Panch, S. R., McManus, A., Bikkani, T., Szymanski, J., Highfill, S. L., Jin, P., Brudno, J., Kochenderfer, J., & Stroncek, D. F. (2019). Effects of starting cellular material composition on chimeric antigen receptor T-cell expansion and characteristics. Transfusion, 59(5), 1755-1764. https://doi.org/10.1111/trf.15287