4-1BB aptamer-based immunomodulation enhances the efficacy of ionizing

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4-1BB aptamer-based immunomodulation enhances the efficacy of ionizing radiation in a preclinical murine tumor model Arm 2 Arm 1 4-1BB RNA aptamer Tumor Volume (mm3) Days Post-Implantation 1

4-1BB aptamer-based immunomodulation enhances the efficacy of ionizing radiation in a preclinical murine tumor model RT  Antigen release  4-1BB expressed on CD8+ T cell surface 4-1BB-mediated anti-tumor response 4-1BB aptamer 4-1BB Kalbasi et al., JCI-2013 2

4-1BB aptamer-based immunomodulation enhances the efficacy of ionizing radiation in a preclinical murine tumor model 4-1BB Antibody or Aptamer Tumor Cells D0 D15 D17 D19 D21 D14 D16 D18 D20 Radiotherapy Fractions Tumor Volume (mm3) Days Post-Implantation * % CD8+/106 cells 5Gyx3 + IgG mAb + 4-1BB + SCR Aptamer 3

TAKE HOME POINTS/FUTURE DIRECTIONS: 4-1BB aptamer-based immunomodulation enhances the efficacy of ionizing radiation in a preclinical murine tumor model TAKE HOME POINTS/FUTURE DIRECTIONS: 4-1BB aptamer-mediated immunomodulation as effective as gold-standard 4-1BB mAb in combination with fractionated radiotherapy Aptamer-mediated 4-1BB activation with radiotherapy does not elicit increased CD8+ T cell infiltrate into liver compared to 4-1BB mAb Future work will determine effect of RT + 4-1BB aptamer in additional murine tumor model systems (i.e. 4T1 post-surgical metastasis model, B16, CT26, MCA, Her2/neu transgenic) Development of human-rhesus macaque cross-reactive 4-1BB aptamer for toxicity studies and clinical translation via proprietary SELEX 4