Abstract
<p>B7H3.CAR EBVSTs effectively target B7-H3–positive solid tumors <i>in vivo</i>. B7H3.CAR EBVST activity in a mouse model of HT-29 colorectal cancer (<b>A–D</b>). <b>A,</b> Body weight measurements posttreatment. <b>B,</b> Tumor volume (left) and fold change (right) after treatment. <b>C,</b> Endpoint absolute tumor cell counts and B7-H3 expression levels quantified by flow cytometry. <b>D,</b> 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 (<b>E–I</b>). <b>E,</b> 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. <b>F,</b> Tumor volume (left) and fold change (right) after treatment. <b>G,</b> 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. <b>H,</b> Body weight measurements posttreatment. <b>I,</b> Kaplan–Meier log-rank survival curve. Mice were euthanized and censored when tumor volume reaches 1,000 mm<sup>3</sup>. <b>J,</b> 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. <b>K,</b> 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 <i>P</i> 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. *, <i>P</i> < 0.05; **, <i>P</i> < 0.01; ***, <i>P</i> < 0.001; ****, <i>P</i> < 0.0001. Error bars denote means ± SD where applicable.</p>
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