Pfizer Corporation

Allogene Therapeutics, Inc.

Allogene Therapeuctics, Inc.

Thomas John Van Blarcom

Barbra Johnson Sasu

Javier Fernando Chaparro Riggers

Siler Panowski

Arvind Rajpal

Tracy Chia-Chien Kuo

Pavel Strop

Roman Galetto

Wei Chen

Yik Andy Yeung

Weihsien Ho

Leila Marie Boustany

Edward Derrick Pascua

Amy Shaw-Ru Chen

Tao Sai

Cesar Adolfo Sommer

Regina Junhui Lin

Surabhi Srivatsa Srinivasan

Philippe Duchateau

Thomas Charles Pertel

Bijan Andre Boldajipour

Yi Zhang

Alexandre Juillerat

Julien Valton

Mathilde Brunnhilde Dusseaux

Niranjana Aditi Nagarajan

Michael Thomas Bethune

Yoon Park

Lidia Mosyak

Edward Roland Lavallie

Chia-Yang Lin

Sheng Ding

Meritxell Galindo Casas

Alison Jane Forgie

Spencer Park

Andrew Ross Nager

Arun Balakumaran

Nguyen Tan

Shanshan Lang

Zhe Li

Jessica Lynn Stanfield

Shahram Salek-Ardakani

Pawel Kamil Dominik

Shih-Hsun Chen

Silvia K Tacheva-Grigorova

Andrea Rossi

A reversibly gated effector polypeptide e.g. a chimeric antigen receptor (protease-activating CD45-gate CAR) comprising an extracellular CD45 recruiting domain, a protease-cleavable linker, and a polypeptide comprising an extracellular ligand binding domain, a transmembrane domain, and an intracellular domain. Nucleic acids including vectors and expression vectors that encode the protease-activating CD45-gate CAR and cells including immune cells such as T cells that comprise and express the nucleic acids. Methods of treatment of various conditions including various forms of cancer comprising administering the cells including CAR T cell therapy. In some embodiments, the CD45 gate at least partially inhibits activation of the protease-activating CD45-gate CAR when the protease-activating CD45-gate CAR binds antigen. The inhibition is at least partially diminished, relieved and/or eliminated when the protease-activating CD45-gate CAR is exposed to a protease that can cleave the linker.

Protease-activating CD45-gate CAR

Provided herein are recombinant antigen receptors, for example chimeric antigen receptors (CARs), that comprise modified cytoplasmic domains that provide improved signalling and thereby provide improved performance and safety. Also provided are polynucleotides encoding the recombinant antigen receptors, vectors comprising the polynucleotides, and engineered immune cells comprising the vectors and/or polynucleotides. The invention further provides methods for engineering immune cells to express the recombinant antigen receptors. Improved recombinant antigen receptor signalling is also provided by co-expressing a first recombinant antigen receptor and a second recombinant antigen receptor or co-expressing a recombinant antigen receptor and a protein involved in transducing the signal from the activated recombinant antigen receptor. Also provided are methods of treating a variety of conditions, including, but not limited to, blood cancers and cancers characterized by solid tumors, by administering the engineered cells to patients suffering from such a condition.

Chimeric antigen receptors with enhanced signaling and activities and uses thereof

The present invention provides inducible chimeric cytokine receptors responsive to a ligand, e.g., a small molecule or protein, uses of such receptors for improving the functional activities of genetically modified immune cells, such as T cells, comprising the inducible chimeric cytokine receptors, and compositions comprising such cells.

Inducible chimeric cytokine receptors

The disclosure provides CARs (CARs) that specifically bind to CD70. The disclosure further relates to engineered immune cells comprising such CARs, CAR-encoding nucleic acids, and methods of making such CARs, engineered immune cells, and nucleic acids. The disclosure further relates to therapeutic methods for use of these CARs and engineered immune cells comprising these CARs for the treatment of a condition associated with malignant cells expressing CD70 (e.g., cancer).

Chimeric antigen receptors targeting CD70

Provided herein are modified caspase-9 polypeptides, and chimeric caspase-9 proteins containing the modified caspase-9 polypeptides. The disclosure further provides polynucleotides encoding these proteins, engineered host cells containing these polynucleotides and proteins, including host cells that co-express a chimeric antigen receptor, and methods of making and using the same.

Modified caspase-9 polypeptides and methods of use thereof

Provided herein are constitutively active chimeric cytokine receptors (CACCRs). When present on chimeric antigen receptor (CAR)-bearing immune cells, such CACCRs allow for increased immune cell activation, proliferation, persistence, and/or potency. Also provided are methods of making and using the CACCRs described herein.

Constitutively active chimeric cytokine receptors

Provided here are engineered immune cells that comprise a constitutively active chimeric cytokine receptor (CACCR) and a B-cell maturation antigen (BCMA) specific chimeric antigen receptor (CAR). Also provided herein are engineered immune cells that comprise one or more nucleic acids e.g. a bicistronic vector such as a viral vector that encode the CACCRs and BCMA CARs and engineered immune cells e.g. engineered autologous or allogeneic T cells that express both CACCRs and BCMA CARs from the nucleic acids. When present on chimeric antigen receptor (CAR)-bearing engineered immune cells, the CACCRs allow for increased immune cell activation, proliferation, persistence, and/or potency. Further provided herein are methods of making and using the engineered immune cells described herein, such as methods of treating a disease or condition by administering at least one appropriate dose of the cells to a patient suffering from the condition.

BCMA CAR-T cells with enhanced activities

The present invention provides antibodies that specifically bind to CD70 (Cluster of Differentiation 70). The invention further provides bispecific antibodies that bind to CD70 and another antigen (e.g., CD3). The invention further relates to antibody encoding nucleic acids, and methods of obtaining such antibodies (monospecific and bispecific). The invention further relates to therapeutic methods for use of these antibodies for the treatment of CD70-mediated pathologies, including cancer.

Antibodies specific for CD70 and their uses

The invention provides CARs (CARs) that specifically bind to BCMA (B-Cell Maturation Antigen). The invention further relates to engineered immune cells comprising such CARs, CAR-encoding nucleic acids, and methods of making such CARs, engineered immune cells, and nucleic acids. The invention further relates to therapeutic methods for use of these CARs and engineered immune cells for the treatment of a condition associated with malignant cells expressing BCMA (e.g., cancer).

Chimeric antigen receptors targeting B-cell maturation antigen

The present invention relates to antibodies, e.g., full length antibodies or antigen binding fragments thereof, that specifically bind to BCMA (B-Cell Maturation Antigen) and/or CD3 (Cluster of Differentiation 3). The invention also relates to antibody conjugates (e.g., antibody-drug-conjugates) comprising the BCMA antibodies, compositions comprising the BCMA antibodies, and methods of using the BCMA antibodies and their conjugates for treating conditions associated with cells expressing BCMA (e.g., cancer or autoimmune disease). The invention further relates to heteromultimeric antibodies that specifically bind to CD3 and a tumor cell antigen, (e.g., bispecific antibodies that specifically bind to CD3 and BCMA). Compositions comprising such heteromultimeric antibodies, methods for producing and purifying such heterodimeric antibodies, and their use in diagnostics and therapeutics are also provided.

Therapeutic antibodies and their uses

Provided herein are PD-1 chimeric cytokine receptors. When present on chimeric antigen receptor (CAR)-bearing immune cells, such receptors allow for increased immune cell activation, proliferation, persistence, and/or potency, when engaged with PD-1 ligands or activation with an anti-PD-1 antibody. Also provided are methods of making and using the chimeric cytokine receptors described herein.

Chimeric cytokine receptors bearing a PD-1 ectodomain

Antibodies that specifically bind to CD47 and antibodies that specifically bind to PD-L1 are provided, as well as CD47/PD-L1 bispecific antibodies. Also provided are uses of these antibodies, and related compositions and methods.

Antibodies specific for CD47, PD-L1, and uses thereof

Provided herein are DLL3 binding agents and chimeric antigen receptors (CARs) comprising a DLL3 binding molecule that specifically binds to DLL3; and immune cells comprising these DLL3-specific CARs, e.g., CAR-T cells. Also provided are methods of making and using DLL3-specific CARs, and immune cells comprising DLL3-specific CARs.

DLL3 targeting chimeric antigen receptors and binding agents

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Oakland, CA, United States of America

Thomas John Van Blarcom