Program Goals. Program Goals Immunotherapy of B-cell Malignancies.

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Presentation transcript:

Program Goals

Immunotherapy of B-cell Malignancies

Evidence of GvL Effect From Allo-BMT

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

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

Autologous T-cell Therapy: Melanoma

Generation of a Tumor-targeted CAR

Evolution in CAR Design

Second-generation CARs: In Vivo

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

Study Design

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

Disease Characteristics and Outcomes

Studies of Relapsed B-cell ALL

CRS and Neurologic Toxicities

CRS Management

CD19 Expression at Baseline and at Relapse

University of Pennsylvania Clinical Trial Results

University of Pennsylvania Clinical Trial Results

Early Clinical Trial Results (NCI)

MSKCC Clinical Trial Results: CLL

The Hostile Tumor Microenvironment

Interleukin-12

IL-12-secreting CAR T Cells In Vivo Efficacy

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

Syngeneic EL4(hCD19) Tumor Model

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

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

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