Patent ID: 10314903

Abstract:
Here we show that SEG/SEI presented from a HLA-DQ8 (HLA-DQB*0302 and HLA-DQA*0301) platform prevent the de novo outgrowth (vaccination) of Lewis lung carcinoma (LLC) and B16-F10 melanoma and retard the growth of established tumors with no significant toxicity. Vaccination of DQ8 tg mice with irradiated LLC or B16-F10 melanoma followed by SEG/SEI immunization and live tumor challenge resulted in 100 and 66% survival respectively for 200 days compared to a median survival of 20 days for untreated controls (p<0.001). In vaccination studies, DQ8 tg mice showed a surge in IFNγ serum levels reaching 3000 fold above baseline devoid of a parallel spike in TNFα levels above baseline levels. Presentation of the SEG/SEI superantigen from a MHC-DQ8 platform, therefore, augments the therapeutic index of these SAgs inducing a tumoricidal response against Lewis lung carcinoma and B16 melanoma accompanied by a sharp increase of therapeutic IFNγ levels absent toxic levels of TNFα.