CD28 and 41BB costimulation enhances the effector function of CD19-specific engager T cells

Mireya Paulina Velasquez, Arpad Szoor, Abishek Vaidya, Aarohi Thakkar, Phuong Nguyen, Meng Fen Wu, Hao Liu, Stephen Gottschalk

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

T cells expressing CD19-specific chimeric antigen receptors (CARs) with endodomains that encode a signaling domain derived from CD3ζ and CD28 or 41BB have potent antitumor activity in early-phase clinical studies for B-cell malignancies. Besides CD19-specific CARs, other approaches are actively being pursued to redirect T cells to CD19, including recombinant bispecific T-cell engager (BiTE) proteins or T cells genetically modified to express BiTEs [engager (ENG) T cells]. As BiTEs provide no costimulation, we investigated here if provision of costimulation through CD28 and 41BB enhances the effector function of CD19-ENG T cells. CD19-ENG T cells expressing CD80 and 41BBL on their cell surface (CD19-ENG.41BBL/CD80 T cells) were generated by retroviral transduction. CD19-ENG.41BBL/CD80 T cells retained their antigen specificity and had superior effector function compared with both unmodified T cells and CD19-ENG T cells expressing either CD80, 41BBL, or no costimulatory molecule, as judged by cytokine (IFNγ and IL2) production, T-cell proliferation, and their ability to sequentially kill target cells. In vivo, CD19-ENG.41BBL/CD80 T cells had superior antileukemia activity in the BV173 xenograft model, resulting in a survival advantage in comparison to CD19-ENG T cells. Thus, provision of costimulation is critical for the effector function of ENG T cells.

Original languageEnglish (US)
Pages (from-to)860-870
Number of pages11
JournalCancer Immunology Research
Volume5
Issue number10
DOIs
StatePublished - Oct 1 2017
Externally publishedYes

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T-Lymphocytes
Heterografts
Interleukin-2
B-Lymphocytes
Cell Proliferation
Cytokines
Antigens

ASJC Scopus subject areas

  • Immunology
  • Cancer Research

Cite this

Velasquez, M. P., Szoor, A., Vaidya, A., Thakkar, A., Nguyen, P., Wu, M. F., ... Gottschalk, S. (2017). CD28 and 41BB costimulation enhances the effector function of CD19-specific engager T cells. Cancer Immunology Research, 5(10), 860-870. https://doi.org/10.1158/2326-6066.CIR-17-0171

CD28 and 41BB costimulation enhances the effector function of CD19-specific engager T cells. / Velasquez, Mireya Paulina; Szoor, Arpad; Vaidya, Abishek; Thakkar, Aarohi; Nguyen, Phuong; Wu, Meng Fen; Liu, Hao; Gottschalk, Stephen.

In: Cancer Immunology Research, Vol. 5, No. 10, 01.10.2017, p. 860-870.

Research output: Contribution to journalArticle

Velasquez, MP, Szoor, A, Vaidya, A, Thakkar, A, Nguyen, P, Wu, MF, Liu, H & Gottschalk, S 2017, 'CD28 and 41BB costimulation enhances the effector function of CD19-specific engager T cells', Cancer Immunology Research, vol. 5, no. 10, pp. 860-870. https://doi.org/10.1158/2326-6066.CIR-17-0171
Velasquez, Mireya Paulina ; Szoor, Arpad ; Vaidya, Abishek ; Thakkar, Aarohi ; Nguyen, Phuong ; Wu, Meng Fen ; Liu, Hao ; Gottschalk, Stephen. / CD28 and 41BB costimulation enhances the effector function of CD19-specific engager T cells. In: Cancer Immunology Research. 2017 ; Vol. 5, No. 10. pp. 860-870.
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