Provided herein are chimeric transmembrane receptor polypeptides configured to oligomerize upon recognition of an extramembrane signal. The receptors include an extramembrane domain, a transmembrane domain, and an intramembrane domain configured to induce activation of one or more intramembrane signal pathways upon oligomerization of the receptor. The provided receptors are particularly useful for engineered cell therapies. Also provided are systems and host cells including the disclosed receptors, and methods for using the disclosed materials.

In various embodiments, the present disclosure provides chimeric antigen receptors (CARs) which bind to mesothelin. The mesothelin CARs comprise an extracellular region comprising a binding domain that specifically binds to at least a portion of mesothelin, a transmembrane region, and an intracellular region comprising an effector domain or a portion or variant thereof and a costimulatory domain or a portion or variant thereof. Recombinant host cells expressing the mesothelin CARs are also provided, as well as compositions and methods of treatment, prevention, and manufacture comprising the same.

A CAR-immunocyte targeting an NKG2D ligand can be used in the preparation of a drug. The drug is used for: (i) removing the senescent cell, the NKG2D ligand in the senescent cell being up-regulated by 2-20 times, preferably 4-15 times, more preferably 10-20 times the normal cell; (ii) delaying individual senescence; and/or (iii) preventing and/or treating age-related diseases. The CAR-immunocyte targeting the NKG2D ligand is capable of specifically removing the senescent cell having high expression of the NKG2D ligand, and has higher in-vivo security.

T cells comprising a molecule comprising (i) a target-specific antigen-binding domain, (ii) an antigen-binding domain that binds a protein associated with a TCR complex, and (iii) a T cell receptor signaling domain polypeptide are provided.

Some embodiments of the methods and compositions provided herein include methods and materials involved in binding a binder (e.g., an antibody, antigen binding fragment, antibody domain, CAR, cell engager, and/or ADC) to an FGFR4 polypeptide. For example, binders (e.g., antibodies, antigen binding fragments, antibody domains, CARs, cell engagers, and/or ADCs) acidic box that bind to an FGFR4 polypeptide and methods and materials for using one or more such binding molecules to treat a mammal (e.g., a human) having cancer are provided. Some embodiments of the methods and compositions provided herein include chimeric antigen receptors (CARs) which specifically bind to fibroblast growth factor receptor 4 (FGFR4). Some embodiments include nucleic acids encoding such CARs, and cells containing such CARs. Some embodiments include the use of such CARs in safe and effective therapies for a cancer, such as an FGFR4-expressing cancer, such as a rhabdomyosarcoma.

An antigen-binding protein targeting CD70. In particular, the present invention relates to a chimeric antigen receptor containing the antigen binding protein and the use thereof, and cells containing or expressing the antigen binding protein. The antigen-binding protein binds to a CD70 protein at 1 nM of a K.sub.D value. The chimeric antigen receptor containing the antigen-binding protein has strong specific recognition and binding abilities to the CD70 protein. The cells containing or expressing the antigen-binding protein can secrete cytokines IL-2 and IFN-.

N(57) Abstract: There is a need for new and alternative options for immune therapy of proliferative diseases such as cancer. This need C\11 may be address by providing a chimeric antigen receptor having an extracellular domain including a binding domain which recognises Nthe cancer-stem-cell-associated protein Lgr5; a transmembrane domain; and an intracellular signalling domain that activates a cellular .,, function. Such CAR T cells can be used to kill cancer cells and treat or prevent cancer in a subject.

The present invention relates to an antibody specific for CD47 and uses thereof, and more particularly, to an antibody that specifically binds to CD47, a chimeric antigen receptor comprising the antibody, and a pharmaceutical composition comprising the same for preventing or treating diseases mediated by CD47-expressing cells.

In the present invention, antibodies that more specifically binds to CD47 were screened to establish 7 new types of antibodies (7C7, 5H4, 5A4, 4E12, 3H3, 3A5, 1E7), and it was confirm that the novel antibodies can specifically binds with CD47 antigen.

In addition, since it was confirmed that the production of a chimeric antigen receptor (CAR) targeting CD47 is possible using the established antibody, the CD47-specific antibody of the present invention and the chimeric antigen receptor prepared using the same can be applied for use in preventing or treating a cancer or tumor expressing CD47.

Provided is an anti-mesothelin chimeric antigen receptor that specifically binds to mesothelin. The anti-mesothelin chimeric antigen receptor according to an aspect exhibits a specific binding ability for mesothelin, and thus, may be useful for preventing or treating cancer in which mesothelin is overexpressed.

Provided is an anti-mesothelin chimeric antigen receptor that specifically binds to mesothelin. The anti-mesothelin chimeric antigen receptor according to an aspect exhibits a specific binding ability for mesothelin, and thus, may be useful for preventing or treating cancer in which mesothelin is overexpressed.