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Blood. 2018 Aug 23;132(8):804-814. doi: 10.1182/blood-2018-01-828343. Epub 2018 Jun 12.

Preinfusion polyfunctional anti-CD19 chimeric antigen receptor T cells are associated with clinical outcomes in NHL.

Author information

1
Kite, a Gilead Company, Santa Monica, CA.
2
IsoPlexis, Branford, CT.
3
Department of Biomedical Engineering, Yale School of Engineering and Applied Science, Yale University, New Haven, CT.
4
Divison of Chemistry and Chemical Engineering, California Institute of Technology, Pasadena, CA; and.
5
Surgery Branch, and.
6
Experimental Transplantation and Immunology Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD.

Abstract

After treatment with chimeric antigen receptor (CAR) T cells, interleukin-15 (IL-15) elevation and CAR T-cell expansion are associated with non-Hodgkin lymphoma (NHL) outcomes. However, the association of preinfusion CAR product T-cell functionality with clinical outcomes has not been reported. A single-cell analysis of the preinfusion CD19 CAR product from patients with NHL demonstrated that CAR products contain polyfunctional T-cell subsets capable of deploying multiple immune programs represented by cytokines and chemokines, including interferon-γ, IL-17A, IL-8, and macrophage inflammatory protein 1α. A prespecified T-cell polyfunctionality strength index (PSI) applied to preinfusion CAR product was significantly associated with clinical response, and PSI combined with CAR T-cell expansion or pretreatment serum IL-15 levels conferred additional significance. Within the total product cell population, associations with clinical outcomes were greater with polyfunctional CD4+ T cells compared with CD8+ cells. Grade ≥3 cytokine release syndrome was associated with polyfunctional T cells, and both grade ≥3 neurologic toxicity and antitumor efficacy were associated with polyfunctional IL-17A-producing T cells. The findings in this exploratory study show that a preinfusion CAR product T-cell subset with a definable polyfunctional profile has a major association with clinical outcomes of CAR T-cell therapy. This trial was registered at www.clinicaltrials.gov as #NCT00924326.

PMID:
29895668
PMCID:
PMC6107882
DOI:
10.1182/blood-2018-01-828343
[Indexed for MEDLINE]
Free PMC Article

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