FIGURE 4 from B7-H3–Targeting Chimeric Antigen Receptors Epstein-Barr Virus–specific T Cells Provides a Tumor Agnostic Off-The-Shelf Therapy Against B7-H3–positive Solid Tumors

Siok Ping Yeo,Lindsay Kua,Jin Wei Tan,Joanna Kristyn Lim,Fiona Hs Wong,May Delos Santos,Chek Meng Poh,Angeline Xh Goh,Xin Yu Koh,Xiaohua Zhou,Ravisankar Rajarethinam,Qingfeng Chen,Zhisheng Her,Ivan D Horak,Lionel Low,Kar Wai Tan

doi:10.1158/2767-9764.25967443

Abstract

B7H3.CAR EBVSTs effectively target B7-H3–positive solid tumors in vivo. B7H3.CAR EBVST activity in a mouse model of HT-29 colorectal cancer (A–D). A, Body weight measurements posttreatment. B, Tumor volume (left) and fold change (right) after treatment. C, Endpoint absolute tumor cell counts and B7-H3 expression levels quantified by flow cytometry. D, Endpoint T-cell counts in blood, liver, lung, spleen, and tumor quantified by flow cytometry. B7H3.CAR EBVST activity was assessed in a breast cancer PDX model (E–I). E, IHC staining of B7-H3 on breast cancer PDX (left) with representative magnified images (right). Brown color represents positive B7-H3 staining. Blue color represents cell nucleus. F, Tumor volume (left) and fold change (right) after treatment. G, Representative IHC staining of B7-H3 and CD3 on tumors from 2 B7H3.CAR EBVST-treated mice and 2 untreated mice. Red color represents positive B7-H3 staining. Brown color represents positive CD3 staining. H, Body weight measurements posttreatment. I, Kaplan–Meier log-rank survival curve. Mice were euthanized and censored when tumor volume reaches 1,000 mm3. J, Experimental scheme to evaluate B7H3.CAR EBVST persistence by performing tumor rechallenge on contralateral flank of mice that had previously cleared NCI-N87 gastric tumors after B7H3.CAR EBVST treatment. K, Volume of NCI-N87 tumors on B7H3.CAR EBVST-treated mice after rechallenge and on control untreated mice. Each curve on the graph represents a mouse. Data comprise of 6–7 (A–D), 9–10 (E–I), and 5 (K) mice in each treatment arm. For A, B, F, H, and K, groups were compared using two-way ANOVA with Tukey test for multiple comparisons test. Comparison and P values between untreated versus UT EBVSTs, untreated versus B7H3.CAR EBVSTs, and UT versus B7H3.CAR EBVSTs groups is represented in black, blue and red, respectively. For C and D, groups were compared using one-way ANOVA with Tukey test for multiple comparisons test. *, P < 0.05; **, P < 0.01; ***, P < 0.001; ****, P < 0.0001. Error bars denote means ± SD where applicable.

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