2. Program Goals

3. Immunotherapy of B-cell Malignancies

4. Evidence of GvL Effect From Allo-BMT

5. Clues to Disease Relapse After Allo-BMT: T cells in Graft and GVHD

6. Autologous Adoptive T-cell Therapy: Tumor-infiltrating Lymphocytes in Melanoma

7. Autologous T-cell Therapy: Melanoma

8. Generation of a Tumor-targeted CAR

10. Evolution in CAR Design

11. Second-generation CARs: In Vivo

12. Phase I: Patients With B-cell ALL Treated With Autologous T Cells Genetically Targeted to CD19

13. Study Design

15. Rapid Tumor Elimination and Recovery of Bone Marrow After 19-28-z CAR T-cell Therapy

16. Disease Characteristics and Outcomes

17. Studies of Relapsed B-cell ALL

18. CRS and Neurologic Toxicities

19. CRS Management

20. CD19 Expression at Baseline and at Relapse

21. University of Pennsylvania Clinical Trial Results

22. University of Pennsylvania Clinical Trial Results

23. Early Clinical Trial Results (NCI)

24. MSKCC Clinical Trial Results: CLL

25. The Hostile Tumor Microenvironment

27. Interleukin-12

29. IL-12-secreting CAR T Cells In Vivo Efficacy

30. IL-12-secreting CAR T Cells Are Resistant to Treg-mediated Inhibition In Vivo

31. Syngeneic EL4(hCD19) Tumor Model

33. 19z1IRESIL-12-modified T Cells Secrete Biologically Active IL-12 and Exhibit Enhanced Targeted Cytotoxic Function and Resistance to Tregs

35. Complete Eradication of ID8(MUC-CD) Ovarian Tumors in Mice With MUC16-targeted T Cells Expressing IL-12

38. Abbreviations

39. Abbreviations (cont)

40. Abbreviations (cont)

41. Abbreviations (cont)

42. Abbreviations (cont)