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 language | English |
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Pages (from-to) | 1-11 |
Number of pages | 11 |
Journal | OncoImmunology |
Volume | 4 |
Issue number | 3 |
DOIs | |
Publication status | Published - 2015 |
Externally published | Yes |
Keywords
- 4–1BB
- B cell lymphoma
- Cancer vaccine
- Hematological malignancies
- Immune checkpoint molecule
- Immunotherapy
- Monoclonal antibody
- NKT cells
- α-galactosylceramide