2. chimeric antigen receptor T-cell therapy for ALL
CD19-targeted

4. Types of Cancer Treatment
Surgery
Chemotherapy
Radiation Therapy
Hormone Therapy
Immunotherapy

5. Types of immunotherapy
Immunotherapy is also sometimes called biologic therapy or biotherapy. It is treatment that uses certain parts of the
immune system to fight diseases such as cancer
Passive immunotherapy
Active immunotherapies

6. Types of Immunotherapy
Monoclonal antibodies
NK cell therapy
DC Therapy
Cytokine
T Cell Therapy

7. 3 major methods for T cell therapy
Tumur Infiltrating Lymphocyte-TILSeparating
The production of T lymphocytes against cancer antigens with genetic engineering
chimeric antigen receptor

8. CAR Construct: What generation is your CAR?

11. Self-driving CAR Safety CAR scFv A scFv A scFv B scFv B CD3 zeta
Costimulatory
domain

12. Advantages of CAR T cell therapy
HLA-independent antigen recognition
Active in both CD4+ and CD8+ T cells
Target antigens include proteins, carbohydrates and glycolipids
Rapid generation of tumor specific T cells
Minimal risk of autoimmunity or GvHD
A living drug

13. CAR Construct: Delivery System
Viral System
Non-Viral System
Lentivirus, retrovirus
Electroportion
Transposon

14. Clinical trials using CD19 targeted T cells
B-ALL

15. CAR Construct: Antigen Selection
CD19 expression is generally restricted to B cells and B cell
precursors1
• CD19 is not expressed on hematopoietic stem cells or other tissue
• CD19 is expressed by most B-cell malignancies
• CLL, B-ALL, DLBCL, FL, MCL Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y
Stem Cell
pro B
pre B
immature B
mature B
plasma cell
CD19
CD22
CD20

17. CART-19
CART-20
CART-22

19. Characteristics of CD19-CAR-Tcell Therapy
Target disease: Relapsed/Refractory B-cell NHL
(Follicular lymphoma, Mantle cell lymphoma, DLBCL)
Clinical trial in 35 patients with ALL
94% Complete remission
More than 80% of the participants were effective
Clinical trial in 45 patients with Non-Hodgkin's Lymphoma

20. TOXICITIES OF CAR T-CELL THERAPY
Fever hypotension
Cytokine release syndrome (CRS)
Neurological toxicity
On-target/off-tumor recognition (aplasia)
Anaphylaxis

21. The Problem
CAR T Toxicities

22. Strategies to Manage CAR Toxicities
inducible caspase 9 (iCasp9) a chimeric protein that binds the small molecule AP1903
leading to caspase 9 dimerization and ultimate apoptosis
engineered to express
“suicide genes

24. CANCER Immunotherapy A NEW HOPE