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Next Generation Chimeric Antigen Receptor (CAR) T Cells
Extended Abstract: 028-MTPIX-01
Next Generation Chimeric Antigen Receptor (CAR) T Cells Introduction T cells may be genetically modified to express chimeric antigen receptors (CAR) targeted to antigens expressed by tumor cells. We have developed this technology in the laboratory and translated this adoptive T cell approach in the clinic. Recently published reports support the novel approach of treating cancer with patient derived T cells genetically modified to express artificial T cell receptors targeted to tumor associated antigens.
Renier Brentjens, MD, PhD Memorial Sloan Kettering Cancer Center, Department of Medicine, New York, NY, USA [email protected]
Results Initial clinical trial outcomes of patients with B cell malignancies treated with autologous T cells genetically modified to express a CAR specific to the CD19 antigen, expressed on most B cell malignancies, demonstrate that this approach may ultimately prove to be a promising therapeutic intervention which will potentially dramatically alter the standard of care in these malignancies. Treatment of patients with CD19 targeted CAR T cells have resulted remarkable remission rates in relapsed B cell acute lymphoblastic leukemia (B-ALL). Specifically, based on currently updated clinical outcomes, we have achieved >85% CR rates in adult patients with relapsed B-ALL treated with CD19 targeted CAR T cells which far exceed historical expectations. Further, by deep sequencing analysis, most treated patients were MRD- after CAR T cell therapy. Significantly, remissions were observed in both patients with overt morphological residual disease at the time of therapy as well as in patients with only residual MRD+ disease. Clinical trials from other centers which confirm the presented clinical trial outcomes from our center will be reviewed. In contrast, far more modest responses were seen in patients with relapsed chronic lymphocytic leukemia (CLL). The discordant clinical outcomes between B-ALL and CLL patients treated with CD19 targeted CAR T cells remains a subject of conjecture although the tumor microenvironment is a strong focus of further investigation. Promising work on pre-clinical studies with “armored” CAR T e cells designed to enhance antitumor efficacy.
Conclusions Furthermore, promising additional T cell genetic modifications based on pre-clinical studies to enhance the efficacy of this CAR modified T cell therapy in second generation clinical trials will be discussed. To this end, we will present novel data on a next generation of CAR T cells, termed “armored CARs” further genetically designed to overcome an immune suppressive tumor microenvironment through further genetic modification of CAR T cells. Promising preclinical studies utilizing these “armored CAR” T cell approaches and their role in future clinical trials will be discussed.
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Next Generation Chimeric Antigen Receptor (CAR) T Cells Introduction T cells may be genetically modified to express chimeric antigen receptors (CAR) targeted to antigens expressed by tumor cells. We have developed this technology in the laboratory and translated this adoptive T cell approach in the clinic. Recently published reports support the novel approach of treating cancer with patient derived T cells genetically modified to express artificial T cell receptors targeted to tumor associated antigens.
Renier Brentjens, MD, PhD Memorial Sloan Kettering Cancer Center, Department of Medicine, New York, NY, USA [email protected]
Results Initial clinical trial outcomes of patients with B cell malignancies treated with autologous T cells genetically modified to express a CAR specific to the CD19 antigen, expressed on most B cell malignancies, demonstrate that this approach may ultimately prove to be a promising therapeutic intervention which will potentially dramatically alter the standard of care in these malignancies. Treatment of patients with CD19 targeted CAR T cells have resulted remarkable remission rates in relapsed B cell acute lymphoblastic leukemia (B-ALL). Specifically, based on currently updated clinical outcomes, we have achieved >85% CR rates in adult patients with relapsed B-ALL treated with CD19 targeted CAR T cells which far exceed historical expectations. Further, by deep sequencing analysis, most treated patients were MRD- after CAR T cell therapy. Significantly, remissions were observed in both patients with overt morphological residual disease at the time of therapy as well as in patients with only residual MRD+ disease. Clinical trials from other centers which confirm the presented clinical trial outcomes from our center will be reviewed. In contrast, far more modest responses were seen in patients with relapsed chronic lymphocytic leukemia (CLL). The discordant clinical outcomes between B-ALL and CLL patients treated with CD19 targeted CAR T cells remains a subject of conjecture although the tumor microenvironment is a strong focus of further investigation. Promising work on pre-clinical studies with “armored” CAR T e cells designed to enhance antitumor efficacy.
Conclusions Furthermore, promising additional T cell genetic modifications based on pre-clinical studies to enhance the efficacy of this CAR modified T cell therapy in second generation clinical trials will be discussed. To this end, we will present novel data on a next generation of CAR T cells, termed “armored CARs” further genetically designed to overcome an immune suppressive tumor microenvironment through further genetic modification of CAR T cells. Promising preclinical studies utilizing these “armored CAR” T cell approaches and their role in future clinical trials will be discussed.
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