NKT cell-targeted vaccination plus anti-4–1BB antibody generates persistent CD8 T cell immunity against B cell lymphoma

Takumi Kobayashi, Brianna L. Doff, Rory C. Rearden, Graham R. Leggatt, Stephen R. Mattarollo*

*Corresponding author for this work

Research output: Contribution to journalArticleResearchpeer-review

26 Citations (Scopus)

Abstract

Harnessing the immune adjuvant properties of natural killer T (NKT) cells is an effective strategy to generate anticancer immunity. The objective of this study was to increase the potency and durability of vaccine-induced immunity against B cell lymphoma by combining a-galactosylceramide (α-GalCer)-loaded tumor cell vaccination with an agonistic antibody targeting the immune checkpoint molecule 4–1BB (CD137). We observed potent synergy when combining vaccination and anti-4–1BB antibody treatment resulting in significantly enhanced survival of mice harboring Eμ-myc tumors, including complete eradication of lymphoma in over 50% of mice. Tumor-free survival required interferon γ (IFNγ)-dependent expansion of CD8+ T cells and was associated with 4–1BB-mediated differentiation of KLRG1C effector CD8+ T cells. ’Cured’ mice were also resistant to lymphoma re-challenge 80 days later indicating successful generation of immunological memory. Overall, our results demonstrate that therapeutic anticancer vaccination against B cell lymphoma using an NKT cell ligand can be boosted by subsequent co-stimulation through 4–1BB leading to a sustainable immune response that may enhance outcomes to conventional treatment.

Original languageEnglish
Pages (from-to)1-11
Number of pages11
JournalOncoImmunology
Volume4
Issue number3
DOIs
Publication statusPublished - 2015
Externally publishedYes

Keywords

  • 4–1BB
  • B cell lymphoma
  • Cancer vaccine
  • Hematological malignancies
  • Immune checkpoint molecule
  • Immunotherapy
  • Monoclonal antibody
  • NKT cells
  • α-galactosylceramide

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