Seattle Children's Hospital

City of Hope

Conagra Foods Rdm, Inc.

University of California

Fred Hutchinson Cancer Center

Purdue Research Foundation

Endocyte, Inc.

Sangamo Biosciences, Inc.

California Institute of Technology

University of Washington

Sangamo Therapeutics, Inc.

Seattle Children's Research Institute

Fred Hutchinson Cancer Research Center

Givaudan S.a.

Wavetronix LLC

Michael C Jensen

James Matthaei

Clinton L Johnson

Stanley R Riddell

Yvonne Y Chen

Jenny Viviana Bermudez Lopez

Eugenia Zah

Kirsten Fletter

Jacqueline Mathews

Adam Brent Johnson

Philip Stewart Low

Michael C Holmes

Philip D Gregory

Christopher Paul Leamon

Andreas Reik

Dale Ando

Yingjuan June Lu

Haiyan Chu

Michael Hudecek

Rebecca Gardner

Leroy W Wheeler, Ii

Susanna Carolina Berger

Courtney Crane

Jia Wei

Kara White Moyes

Nicole Lieberman

Andrew M Scharenberg

Christina D Smolke

Anna M Wu

Adam Johnson

Stephen J Forman

David V Arnold

Jonathan L Waite

David J Rawlings

Gordon Smith

Kamila Sabina Gwiazda

Logan Carl Harris

Andrew A Raubitschek

Suzie H Pun

Tyler Scott Wright

Lance Schilmoeller

Alexandra E Grier

Joshua Gustafson

Nataly Kacherovsky

James Wesley Belleson

Shawn Fear

Richard Messmann

Giacomo Tampella

Navin Robert Charles Pinto

Julie Ruggieri Park

Tracy Ooi

John B Dougall

Thomas William Karlinsey

Ryan Smith

Carolina Berger

Gordon Lee Smith

Tyler S Wright

Suzie Pun

Embodiments of the disclosure include methods of manufacturing compositions comprising host cells. In some alternatives, a method comprises introducing into a host cell an isolated nucleic acid, such as a nucleic acid coding for an isolated polypeptide of an extracellular domain (ECD) of HER2 polypeptide. Some embodiments include culturing the host cells in a medium comprising at least one growth factor. Some embodiments include selecting the host cells for expression of ECD.

Transgene genetic tags and methods of use

A non-immunogenic selection epitope may be generated by removing certain amino acid sequences of the protein. For example, a gene encoding a truncated human epidermal growth factor receptor polypeptide (EGFRt) that lacks the membrane distal EGF-binding domain and the cytoplasmic signaling tail, but retains an extracellular epitope recognized by an anti-EGFR antibody is provided. Cells may be genetically modified to express EGFRt and then purified without the immunoactivity that would accompany the use of full-length EGFR immunoactivity. Through flow cytometric analysis, EGFRt was successfully utilized as an in vivo tracking marker for genetically modified human T cell engraftment in mice. Furthermore, EGFRt was demonstrated to have cellular depletion potential through cetuximab mediated antibody dependent cellular cytotoxicity (ADCC) pathways. Thus, EGFRt may be used as a non-immunogenic selection tool, tracking marker, a depletion tool or a suicide gene for genetically modified cells having therapeutic potential.

Truncated epiderimal growth factor receptor (EGFRt) for transduced t cell selection

The coating can have a low-sweetness perception. During manufacturing and processing, the coating maintains a flowability to allow a glaze state of the coating to be applied to a food. Upon cooling, the glaze state of the coating forms a glass state that provides a low-sweetness impact which facilitates application of savory taste perceptions.

Food product and coating

Aspects described herein pertain to engineered chimeric antigen receptors (CARs) and compositions thereof having specificity and affinity for fluorescein containing ligands presented on the surface of tumor cells. Also provided herein are compositions including CARs further comprising a spacer arm and methods of making and using these compositions.

Fluorescein-specific cars exhibiting optimal t cell function against FL-PLE labelled tumors

The present disclosure relates to methods of treating a patient with a cancer by administering to the patient a composition comprising CAR T cells wherein the CAR T cells comprise a CAR and the CAR comprises an E2 anti-fluorescein antibody fragment, and administering to the patient a small molecule linked to a targeting moiety by a linker. The disclosure also relates to compositions for use in such methods.

Methods of use for CAR T cells

Aspects of the invention described herein include methods of treating, inhibiting, ameliorating and/or eliminating a virus or cancer cells in a subject utilizing genetically engineered human T-cells having receptors for a molecule presented by the virus or the cancer cells, wherein the genetically engineered T cells are isolated utilizing a two-stage MTX selection that employs increasing concentrations of MTX.

Production of engineered T-cells by sleeping beauty transposon coupled with methotrexate selection

The present disclosure relates to methods of treating a patient with a cancer by administering to the patient a composition comprising CAR T cells and administering to the patient a small molecule linked to a targeting moiety by a linker. The disclosure also relates to compositions for use in such methods.

Sequencing method for CAR T cell therapy

A CD20-OR-CD19 chimeric antigen receptor (CAR) protein construct is provided. Also provided are nucleic acids encoding the CD20-OR-CD19 CAR; and methods of use, e.g. in the treatment of B cell malignancies. The CD20-OR-CD19 CAR of the invention is a bispecific CAR that can trigger T-cell activation upon detection of either CD19 or CD20 (or both). It is a single molecule that confers two-input recognition capability upon human T cells engineered to stably express this CAR.

Bispecific or-gate chimeric antigen receptor responsive to CD20 and CD19

Bispecific OR-gate chimeric antigen receptor responsive to CD20 and CD19

The present invention provides nucleic acids, vectors, host cells, methods and compositions to confer and/or augment immune responses mediated by cellular immunotherapy, such as by adoptively transferring CD8+ central memory T cells or combinations of central memory T cells with CD4+ T cells that are genetically modified to express a chimeric receptor under the control of an inducible promoter. In some alternatives the genetically modified host cell comprises a nucleic acid comprising a polynucleotide coding for a chimeric antigen receptor comprising a ligand binding domain, a polynucleotide comprising a spacer region, a polynucleotide comprising a transmembrane domain, and a polynucleotide comprising an intracellular signaling domain under the control of a drug inducible promoter. Controlling the expression of the chimeric receptor provides for the ability to turn expression on and off depending on the status of the patient. Pharmaceutical formulations produced by the method, and methods of using the same, are also described.

Drug regulated transgene expression

Some embodiments provided herein relate to methods and compositions for making genetically modified T cells. In some such embodiments, CD4+ and CD8+ T cells are cultured in a single serum-free volume. In some embodiments, co-cultured CD4+ and CD8+ T cells can be transduced with a lentiviral vector, and a population of transduced T cells can be harvested within a shorter period of time than other conventional methods.

Closed-system manufacturing process for CAR-T cells

Embodiments of the methods and compositions provided herein relate to chimeric antigen receptors (CARs) that specifically bind to B7H3. Some embodiments relate to cell-based immunotherapy targeting tumors, such as tumors comprising B7H3+ cells.

Methods and compositions comprising B7H3 chimeric antigen receptors

Some embodiments of the methods and compositions provided herein relate to chimeric antigen receptors (CARs) that specifically bind to human extracellular domains of the IL-13 alpha 2 (IL13Ra2) receptor, cells containing such CARs, and methods of cell-based immunotherapy targeting cancer cells, such as cells of solid tumors.

Nucleic acids encoding IL-13 receptor alpha 2 (IL13Ra2) chimeric antigen receptor for tumor specific T cell immunotherapy

Provided are methods for preventing or ameliorating toxicity caused by or due to a therapy, such as an immunotherapy or a cell therapy, by pre-emptive or early administration toxicity-targeting agent(s). In some embodiments, the therapy is a cell therapy in which the cells generally express recombinant receptors such as chimeric receptors, e.g., chimeric antigen receptors (CARs) or other transgenic receptors such as T cell receptors (TCRs). Features of the methods, including the timing of the administration of the agents or treatments for toxicity, provide various advantages, such as lower toxicity while maintaining persistence and efficacy of the administered cells.

Early intervention methods to prevent or ameliorate toxicity

The invention is directed to a bispecific chimeric antigen receptor, comprising: (a) at least two antigen-specific targeting regions; (b) an extracellular spacer domain; (c) a transmembrane domain; (d) at least one co-stimulatory domain; and (e) an intracellular signaling domain, wherein each antigen-specific targeting region comprises an antigen-specific single chain Fv (scFv) fragment, and binds a different antigen, and wherein the bispecific chimeric antigen receptor is co-expressed with a therapeutic control. The invention also provides methods and uses of the bispecific chimeric antigen receptors.

Bispecific chimeric antigen receptors, encoding polynucleotides and use of receptors thereof to treat cancer

Growing community of inventors

Bainbridge Island, WA, United States of America

Michael C Jensen