Fred Hutchinson Cancer Center

St Phi Therapeutics Co., Ltd.

Fred Hutchinson Cancer Research Center

Lingfeng Liu

Stanley R Riddell

A series of recombinant DNA constructs and a method is disclosed for use in immunological therapy in general; and in disrupting T cell receptor (TCR), human leukocyte antigens (HLA) class I and NKG2D (Natural-Killer Group 2, member D) ligand expression in particular, with the effect of producing highly compatible autologous universal T cells for further genetically engineering for allogeneic administration. A Universal T (UT) construct is provided and used, comprising a TCR antibody fragment fused to a transmembrane domain (TMD) and ER retention domain of adenovirus early region 3 glycoprotein E3-19k (E3/19K) (TCR-E3/19K RD). The Universal T (UT) construct can hijack ERAD machinery to arrest TCR and HLA molecules in endoplasmic reticulum (ER) and facilitate their translocation into the cytoplasm for ubiquitination and degradation by proteasomes.

Universal T cells and the method of use thereof

The present disclosure relates to tagged chimeric effector molecules and receptor molecules thereof for genetically engineering a host cell, wherein the recombinant host cell can be identified, isolated, sorted, induced to proliferate, tracked or eliminated. For example, a T cell may be recombinantly modified for use in adoptive immunotherapy.

Tagged chimeric effector molecules and receptors thereof

The present disclosure relates to tagged chimeric effector molecules and receptor molecules thereof for genetically engineering a host cell, wherein the recombinant host cell can be identified, isolated, sorted, induced to proliferate, tracked or eliminated using the tag. An exemplary receptor molecule is a chimeric antigen receptor (CAR) having an extracellular domain comprising a binding domain for a target, a hinge region, and a tag cassette, a hydrophobic portion as a transmembrane domain and an intracellular part with an effector domain. An exemplary target is CD19. An exemplary tag is a Strep Tag&#xae;. T cells recombinantly modified for expression of such molecules may be used in adoptive immunotherapy.

Growing community of inventors

Seattle, WA, United States of America

Lingfeng Liu