1. Identification of PD1 and TIM3 As Checkpoints That Limit Chimeric Antigen Receptor T Cell Efficacy in Leukemia 
Saad S. Kenderian, MD, Marco Ruella, MD, Olga Shestova, PhD, Michael Klichinsky, PharmD, Miriam Kim, MD, David L. Porter, MD, Carl H. June, MD, Saar Gill, MBBS, PhD 
Biology of Blood and Marrow Transplantation 
Volume 22, Issue 3, Pages S19-S21 (March 2016)
DOI: /j.bbmt
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2. Figure 1
A) PDL is up-regulated on primary AML cells 24 hours after co-culture with CART33 or CART123 cells B) PD1 is up-regulated on CAR + cells (CART33 or CART 123) after co-culture with primary AMI C) TIM3 is up-regulated on CAR + cells (CART33 or CART123) after co-culture with primary AML
Biology of Blood and Marrow Transplantation  , S19-S21DOI: ( /j.bbmt )
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3. Figure 2
A) NSG mice were injected with MOLM14 AML cell line (1×108 IV) Engraftment was confirmed on Day 6 by bioluminescence imaging AML xenografts were then treated with suboptimal doses CART123 (0.5×106 IV) and followed with serial imaging. Relapsed disease was observed in 60% of AML xenografts B) T cells isolated from bone marrows of relapsed mice after CART cell therapy express higher levels of TIM3 compared to T cells isolated from bone marrows of mice in remission. C) Co-culture of T cells isolated From relapsed mice with TIM3 and PD1 inhibitors (10 ug/ml for 72 hours), in the presence of the antigen target results in improvement of cytokine production and Ki-67 proliferation marker
Biology of Blood and Marrow Transplantation  , S19-S21DOI: ( /j.bbmt )
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4. Figure 3
Combination of CARTs and checkpoint inhibitors in AML xenografts. MOLM14 engrafted xenografts were treated with suboptimal doses of CART 123 in combination with PD1 inhibitors, TIM3 inhibitors or the combination of both antibodies. Antibodies were given on day 3,6,9, and 12 post T cells at a dose of 10mg/kg/dose. The combination of checkpoint blockade and CARTs resulted in synergistic anti-leukemic effect.
Biology of Blood and Marrow Transplantation  , S19-S21DOI: ( /j.bbmt )
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