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

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.