Described herein are immune cells comprising: a T-cell receptor (TCR) and a chimeric stimulating receptor (CSR) that comprises (i) a ligand-binding module that is capable of binding or interacting with a target ligand; (ii) a transmembrane domain; and (iii) a CD30 costimulatory domain, in which the CSR in the immune cells lacks a functional primary signaling domain. Also provided herein are methods of using the same or components thereof (e.g., the CSR) for therapeutic treatment of cancers (e.g., solid tumor cancers).

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.

The present invention provides recombinant TIM-4 fusion proteins comprising an extracellular domain of TIM-4 and at least one co-stimulatory domain. Also provided are cells comprising the fusion protein and methods of making and using the same.

Methods are provided for generating DLL4-expressing immune cells. The invention also includes cellular compositions of dendritic and T cells produced by these methods. The immune cells of the invention can be used widely as components in many diagnostic and therapeutic systems, including improved vaccines to reduce the risk of graft versus host disease.

The presently disclosed subject matter provides methods and compositions for treating myeloid disorders (e.g., acute myeloid leukemia (AML)). It relates to immunoresponsive cells bearing antigen recognizing receptors (e.g., chimeric antigen receptors (CARs)) targeting AML-specific antigens.