The invention provides methods and compositions for use in treating cancer, which advantageously may be achieved by targeting of the tumor microenvironment.

Provided are genetically modified NK cells expressing a chimeric antigen receptor targeting an EGFR superfamily receptor. The CAR can comprise an intracellular domain of FcRI and further recombinant proteins expressed by the genetically modified NK cells are CD16, autocrine growth stimulating cytokines, and optionally one of IL-12, a TGF-beta trap, or a homing receptor. Also described are methods for treating a patient having or suspected of having a disease that is treatable with NK-92 cells, such as cancer, comprising administering to the patient the genetically modified NK cells.

The present disclosure provides improved compositions for adoptive T cell therapies for treating, preventing, or ameliorating at least one symptom of a cancer, infectious disease, autoimmune disease, inflammatory disease, and immunodeficiency, or condition associated therewith.

The invention relates to a T cell expressing an antibody or comprising the coding sequence of the antibody or an expression vector thereof; the antibody contains an optional signal peptide, an antigen binding sequence and a mutant type Fc segment, wherein the mutant type Fc segment is a Fc segment in which amino acid residues at the 17th site and the 79th site of the IgG4 Fc segment shown by SEQ ID NO: 25 are mutated into E and Q respectively. Preferably, the T cell is a CAR-T cell. The present invention further relates to a treatment application of the T cell in malignant tumors.

The present application relates to an antibody capable of specifically binding to c-Met or antigen-binding fragment thereof, and an immunoconjugate, a pharmaceutical composition and a multispecific molecule comprising the same. The present application further relates to the use of the antibody specifically binding to c-Met or an antigen-binding fragment thereof and the multispecific molecule. Compared with the control antibody, the bispecific antibody or defucosylated bispecific antibody of the present application can block HGF-dependent TKI resistance; block the proliferation and migration of tumor cells induced by HGF, induce ADCC effect, and inhibit tumor growth in vivo.

Provided herein, inter alia, are PD-L1(+) natural killer cells that express soluble IL-15, PD-L1(+) natural killer cells that express soluble IL-15 and truncated EGFR, and methods of treating cancer using the PD-L1(+) natural killer cells. In an aspect is provided a method of treating cancer in a patient in need thereof comprising administering to the patient an effective amount of PD-L1(+) natural killer cells that express soluble IL-15.

Described are immune cells expressing a chimeric antigen receptor targeted to EGFR and having an oxygen-dependent degradation domain. The chimeric antigen receptor is co-expressed in immune cells, e.g., NK cells with a soluble form of human IL-15. The inclusion of an oxygen-dependent degradation domain substantially restricts the activity of the immune cells expressing the chimeric antigen receptor to the more hypoxic environment of solid tumor tissue. The NK cells expressing the chimeric antigen receptor are useful for treating breast cancer that has low or no HER2 expression.

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.

A chimeric polypeptide, containing a binding peptide that can specifically bind to a target molecule, a receptor regulatory domain containing one or more cleavage sites, and an intracellular domain. The receptor regulatory domain comprises an extracellular region and a transmembrane region, wherein the extracellular region and the transmembrane region are not both derived from a Notch protein. The binding of the binding peptide to the target molecule can induce the cleavage of the receptor regulatory domain, thereby releasing the intracellular domain.

Provided herein are biepitopic or bispecific chimeric antigen receptors. The chimeric antigen receptors comprise a combination of single domain antibody mimics. The single domain antibody mimics may be monobodies, affibodies, or DARPins. The disclosed chimeric antigen receptors may recognize two different epitopes of the same tumor antigen. For example, the chimeric antigen receptor may recognize two different epitopes of HER-2 or EGFR. The disclosed chimeric antigen receptors may recognize two epitopes of two different tumor antigens. For example, the chimeric antigen receptor may recognize HER-2 and EGFR. The disclosed chimeric antigen receptors may be expressed in immune cells for use in cancer immunotherapy.