Improving the efficacy and safety of adoptive cellular therapies

Abstract

The disclosure relates generally to the generation and use of immune effector cells (e.g., T cells, NK cells) engineered to express an immune receptor (e.g., Chimeric Antigen Receptor, Synthetic Immune Receptor, T Cell Receptor etc.) to treat a disease associated with expression of a target antigen.

Description

[0001] Cross References to Related Applications [0002] This application claims priority to U.S. Provisional Application No. 62 / 712,102, filed July 30, 2018, the disclosure of which is incorporated herein by reference in its entirety. [0003] sequence listing [0004] This application contains a Sequence Listing, which has been filed electronically in ASCII format, and is hereby incorporated by reference in its entirety. Said ASCII copy titled "SEQ-1-3059_ST25" was created on July 30, 2019, and is 4,053,956 bytes in size. technical field [0005] The present disclosure generally relates to the use of immune effector cells (eg, T cells, NK cells) genetically engineered to express chimeric antigen receptors (CARs) for the treatment of diseases associated with tumor antigen expression. Background technique [0006] Adoptive cell transfer (ACT) therapy using immune cells, particularly T cells transduced with chimeric antigen receptors (CARs) and recombinant TCRs, has shown p...

AI Technical Summary

Problems solved by technology

However, administration of lymphocyte-depleting chemotherapy is associated with significant toxicity (eg, pancytopenia, fever, risk of infection, neurotoxicity) and death

Additionally, adoptively transferred T cells failed to reproduce despite administration of lymphocyte-depleting chemotherapy

A problem associated with adoptively transferred immune cells is excessive stimulation and proliferation, which is associated with toxicities such as cytokine release syndrome, neurotoxicity (including death)

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