Fig. 6: Combinatorial immunotherapy in vivo using viral-vector-mediated CaDox delivery.
From: Tumour priming by ultrasound mechanogenetics for CAR T therapy
a,e, Schematic representation of experimental timelines for two different gene and T cell delivery approaches used to evaluate the therapeutic efficacy of the FUS controllable cell immunotherapy. In a, NSG mice with bilateral PC-3 tumours received peritumoural AAV-mediated CaDox delivery, followed by local FUS activation and peritumoural T cell administration. In e, an alternative strategy employed systemic lentiviral delivery of the CaDox circuit, followed by local FUS activation and systemic T cell administration. i.v., intravenous. b,f, IVIS imaging of tumour bioluminescence at multiple time points to compare tumour burden across treatment groups. In b, mice received local AAV-CaDox injection, whereas in f, mice received systemic injections of lentiviral CaDox constructs and CAR T cells. c,g, Quantification of luciferase signal intensity normalized to pretreatment levels over time. Adjusted P values at the end-point are as follows: in c, P = 0.0042; in g, P < 0.0001. d,h, Tumour volume measurements over time using caliper-based assessments. Adjusted P values at end-point are as follows: in d, P = 0.0076; in h, P = 0.0037. Each line represents the group mean ± s.e.m. (n = 4 mice per group). Statistical significance was determined using two-way ANOVA with Tukey’s multiple comparisons test (two-sided). ** and **** denote adjusted P < 0.01 and P < 0.0001, respectively. Panels a and e created with BioRender.com.
