| First Author | Mattarollo SR | Year | 2012 |
| Journal | Blood | Volume | 120 |
| Issue | 15 | Pages | 3019-29 |
| PubMed ID | 22932803 | Mgi Jnum | J:192928 |
| Mgi Id | MGI:5466820 | Doi | 10.1182/blood-2012-04-426643 |
| Citation | Mattarollo SR, et al. (2012) NKT cell adjuvant-based tumor vaccine for treatment of myc oncogene-driven mouse B-cell lymphoma. Blood 120(15):3019-29 |
| abstractText | Immunomodulators are effective in controlling hematologic malignancy by initiating or reactivating host antitumor immunity to otherwise poorly immunogenic and immune suppressive cancers. We aimed to boost antitumor immunity in B-cell lymphoma by developing a tumor cell vaccine incorporating alpha-galactosylceramide (alpha-GalCer) that targets the immune adjuvant properties of NKT cells. In the Emu-myc transgenic mouse model, single therapeutic vaccination of irradiated, alpha-GalCer-loaded autologous tumor cells was sufficient to significantly inhibit growth of established tumors and prolong survival. Vaccine-induced antilymphoma immunity required NKT cells, NK cells, and CD8 T cells, and early IL-12-dependent production of IFN-gamma. CD4 T cells, gamma/delta T cells, and IL-18 were not critical. Vaccine treatment induced a large systemic spike of IFN-gamma and transient peripheral expansion of both NKT cells and NK cells, the major sources of IFN-gamma. Furthermore, this vaccine approach was assessed in several other hematopoietic tumor models and was also therapeutically effective against AML-ETO9a acute myeloid leukemia. Replacing alpha-GalCer with beta-mannosylceramide resulted in prolonged protection against Emu-myc lymphoma. Overall, our results demonstrate a potent immune adjuvant effect of NKT cell ligands in therapeutic anticancer vaccination against oncogene-driven lymphomas, and this work supports clinical investigation of NKT cell-based immunotherapy in patients with hematologic malignancies. |
