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. Author manuscript; available in PMC: 2022 Nov 30.
Published in final edited form as: Nat Cancer. 2022 May 30;3(7):808–820. doi: 10.1038/s43018-022-00383-0

Figure 6. Increased efficacy of CAR T cells engineered to inactivate PARP11.

Figure 6.

A. Schematic representation of shCON and shPARP11-CD19-BBz chimeric receptors.

B. Flow cytometry analysis of levels of IFNAR1 on the surface of indicated CAR T cells treated with or without adenosine (Ado, 1mM, 24h). Statistical analysis was performed using ordinary one-way ANOVA with Tukey`s multiple comparisons test. **P = 0.0033, ***P = 0.0009. n = 5 samples.

C. Lysis of hCD19-B16F10 cells by shCON-CD19-BBz or shPARP11-CD19-BBz CAR T cells treated with or without adenosine (Ado, 1mM, 24h). (E:T ratio=10:1). Statistical analysis was performed using ordinary one-way ANOVA with Tukey`s multiple comparisons test. ****P < 0.0001. n = 6 independently treated cell cultures.

D. Lysis of NALM6 cells that express endogenous CD19 by shCON-CD19-BBz or shPARP11-CD19-BBz CAR T cells treated with or without adenosine (Ado, 1mM, 24h). (E:T ratio=10:1). Statistical analysis was performed using ordinary one-way ANOVA with Tukey`s multiple comparisons test. ****P < 0.0001, *P = 0.0426. n = 6 independently treated cell cultures.

E. hCD19-B16F10 tumor growth in NSG mice inoculated with 5×105 hCD19-B16 cells (s.c.) and 7 days later administered with indicated CAR T cells (1×106/ mouse, i.v). Statistical analysis was performed using two-way ANOVA with Tukey`s multiple comparisons test. ****P < 0.0001, ***P = 0.0005. Con, n = 4 mice; shCon, n = 5 mice; shPARP11, n = 5 mice.

F. The Kaplan-Meier analysis of survival of animals from experiment described in Fig 6E (Con, n = 4 mice; shCon, n = 5 mice; shPARP11, n = 5 mice). Statistical analysis was performed using Log-rank (Mantel-Cox) test. *P = 0.0138, **P = 0.0026.

G. Growth of EM-Meso-GFP-Luc tumors (1×106/mouse, s.c.) in NSG mice that were administered with control (PBS) or WT or PARP11 knockout Meso-BBz CAR T cells (1×106/ mouse, i.v. on day 7). Statistical analysis was performed using two-way ANOVA with Tukey`s multiple comparisons test. ****P < 0.0001. n=5 mice.

H. The Kaplan-Meier analysis of survival of animals from experiment described in Fig. Statistical analysis was performed using Log-rank (Mantel-Cox) test. **P = 0.0019, *P = 0.0174. n = 5 mice.