1. 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

2. 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

3. 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

4. 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