Fig. 7: mRIPO(H3.3) immunization extends survival in an intracerebral glioma model.
a, b CT2A cells were transduced with HLA-A2 (AAD) (a) and full-length mouse histone 3.3(K27M) (b). DIPG 36 is a human H3.3K27M + DIPG cell line used as a positive control. c, d AAD_hCD155 transgenic mice express HLA-A2 (AAD) in splenocytes (c) and hCD155 (in brain; d). HeLa cells were used as a positive control (the differences in hCD155 electrophoretic mobility are due to differential glycosylation). e AAD_hCD155 transgenic mice were immunized by i.m. inoculation (day 1), implanted with CT2A_AADH3.3K27M cells for orthotopic tumor initiation (day 7), boosted with the same regimen (day 14), and followed for assessment of weight and neurological status. Mice were euthanized after losing 15% of their max. weight. mRIPO(H3.3)-immunized mice survived significantly longer than their mRIPOδ6-immunized littermates [P = 0.0121, Log-rank (Mantel-Cox) test; mRIPOδ6 n = 9 animals, mRIPO(H3.3) n = 10]. A replicate is shown in Supplementary Fig. 19. (f) CD8 depletion abrogates the anti-tumor effect of mRIPO(H3.3) immunization. The assay was performed as in (e), with CD8 depletion antibody administered every 4 days starting at 7 days prior to tumor implantation [P = 0.3493, Log-rank (Mantel-Cox) test; mRIPOδ6 + αCD8 n = 10 animals; mRIPO(H3.3) + αCD8 n = 11].
