Journal
ONCOIMMUNOLOGY
Volume 4, Issue 3, Pages -Publisher
TAYLOR & FRANCIS INC
DOI: 10.4161/2162402X.2014.990793
Keywords
alpha-galactosylceramide; B cell lymphoma; cancer vaccine; hematological malignancies; immunotherapy; immune checkpoint molecule; monoclonal antibody; NKT cells; 4-1BB
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Funding
- National Health and Medical Research Council (NHMRC) of Australia [APP1044355]
- Leukemia Foundation of Australia
- NHMRC Career Development Fellowship [APP1061429]
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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 (alpha-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 E mu-myc tumors, including complete eradication of lymphoma in over 50% of mice. Tumor-free survival required interferon gamma (IFN gamma)-dependent expansion of CD8(+) T cells and was associated with 4-1BB-mediated differentiation of KLRG1(+) 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.
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