Figure 7. Combination Immunotherapies Triggered by Cancer-Specific Circuits Significantly Reduced Tumor Burden and Increased Survival in an Intraperitoneally Disseminated Human Ovarian Cancer Model in Mice.

(A) OV8 cells were transduced with constructs encoding a control output rtTA3 (Control), STE-only (STE), or combination immunomodulators (SCIP). All groups were implanted into NSG mice and injected periodically with human T cells. Student’s t test was performed to compare tumor burden between groups at day 37.

(B) Kaplan-Meier survival curves of various groups. A log-rank (Mantel-Cox) test was performed to compare survival between groups.

(C) Robust therapeutic efficacy was achieved even when only 15% or 30% of tumor cells were transduced with the SCIP. Student’s t test was performed to compare tumor burden between groups at day 41.

(D) Kaplan-Meier survival curves of various groups with different percentages of the overall tumor cells transduced with the SCIP circuit. A log-rank (Mantel-Cox) test was performed to compare survival between groups.

(E) Lentiviral delivery of the SCIP-expressing circuit significantly reduced ovarian cancer burden. NSG mice were injected with OV8 cells into the peritoneal space at day 0. Lentiviruses encoding circuit module 1 and module 2 and a control output rtTA3 (Control), or combination immunomodulators (SCIP) were then injected i.p. on day 7. These mice were also injected i.p. periodically (days 9, 16, and 23) with human T cells. Student’s t test was performed to compare tumor burden between groups at day 39.

(F) Kaplan-Meier survival curves of various groups. A log-rank (Mantel-Cox) test was performed to compare survival between groups.

Error bars represent SEM, n = 5 biological replicates for all experiments, except n = 4 biological replicates for groups in (C–D).

(^*p < 0.05; **p < 0.005).

See also Figure S5, S6, and S7.