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. Author manuscript; available in PMC: 2021 Jan 17.
Published in final edited form as: Sci Transl Med. 2019 Jun 26;11(498):eaaw2614. doi: 10.1126/scitranslmed.aaw2614

Fig. 3. Collagen-anchoring IL-12 demonstrates reduced toxicity and potentiates disparate systemic immunotherapy modalities.

Fig. 3.

Mice were inoculated with 1x106 B16F10 cells on day 0. (A) Weight change from baseline and (B) corresponding survival of these mice after treatment with intratumoral (i.tu.) injections of PBS (n = 6), IL12-MSA (n = 7), or IL12-MSA-Lumican (n = 7), or intraperitoneal (i.p.) injection of IL12-MSA (n = 7) on days 6 and 12. Weight change for entire group plotted until a mouse in that group reaches the euthanasia criterion. (C) Mice were inoculated with 1x106 B16F10 cells on day 0. Vaccinations (Vacc) were administered subcutaneously (s.c.) at the tail base. The graphs show weight change from baseline (left, mean + S.D.), corresponding tumor area (middle, mean + S.D.), and survival (right) of mice treated with i.tu. injections of PBS (n = 12), IL-12 (n = 10 for IL12-MSA; n = 10 for IL12-MSA-Lumican), vaccine (n = 7) alone, or vaccine and IL12 (n = 7 for IL12-MSA; n = 7 for IL12-MSA-Lumican) on days 5, 11, and 17. (D) Mice were inoculated with 0.5 x106 B16F10 cells on day 0 and lymphodepleted by total body irradiation on day 4. CAR-T treatments using 10 million CD3+ CAR-T cells were injected through the tail vein (i.v.) only on day 5. The graphs show weight change from baseline (left, mean + S.D.), corresponding tumor area (middle, mean + S.D.), and survival (right) of mice treated with intratumoral (i.tu.) injections of PBS (n = 11), IL-12 (n = 9 for IL12-MSA; n = 5 for IL12-MSA-Lumican), CAR-T (n = 11) alone, or CAR-T and IL12 (n = 9 for IL12-MSA; n = 5 for IL12-MSA-Lumican) on days 5 and 11. (E) Mice were inoculated with 0.5 x106 4T1-Luc cells in the mammary fat pad on day 0. Neoadjuvant therapy was administered on days 7 and 13 and the primary tumors was surgically excised on day 16. Post-operation, mice were monitored for metastases by in vivo imaging. The graphs show total body weight change during neoadjuvant treatment (left), primary tumor growth and weight (middle), and metastasis-free survival (right) of mice left untreated (n = 10) or treated with intratumoral (i.tu.) injections of IL-12 (n = 10 for scIL12; n = 9 for IL12-MSA-Lumican) and intraperitoneal (i.p.) injection of anti-PD-1 on day 7 and 13. Arrowheads indicate times of treatment. Tumor area for each group shown until a mouse in that group reaches the euthanasia criterion or primary tumor is excised. Weight change shown until a mouse in study reaches the euthanasia criterion or primary tumor is excised. Weight changes and excised tumor weights were compared by one-way ANOVA with Tukey’s multiple comparison test. Survival was compared by log-rank Mantel-Cox test. *, P < 0.03; **, P < 0.002; ***, P < 0.0002; ****, P < 0.0001; n.s., not significant.