Provided herein is a composition comprising, a cell, comprising nucleic acids encoding a chimeric antigen receptor (CAR) and one or more of signaling proteins selected from K13-vFLIP, MC159-vFLIP, cFLIP-L, cFLIP-p22, HTLV1-Tax and HTLV2-Tax, wherein the CAR comprises an a) extracellular antigen specific domain, b)a transmembrane domain and c) an intracellular signaling domain comprising an immunoreceptor tyrosine-based activation motif (ITAM); wherein c) is located at the C-terminus of the chimeric receptor. In some embodiments, the CAR further comprises one or more co-stimulatory domains. Also provided herein are methods for treating diseases using the compositions described herein.

Provided herein are chimeric receptors, engineered cells and pharmaceutical compositions for enhancement of long-term clearance of protein aggregates in the central nervous system via phagocytosis or engulfment. Further provided herein are methods of treatment of subjects suffering from, or diagnosed with, a neurodegenerative disease by administering these receptors, modified cells, and/or pharmaceutical compositions. Administration of one or more, or a plurality of these modified cells, to a subject may provide treatment of a neurodegenerative disease such as Alzheimer's Disease (AD) or Parkinson's Disease (PD). Advantageously, the modified cells, pharmaceutical compositions, and methods of the present disclosure meet existing needs in the art by providing clearance of accumulations of protein aggregates in brain tissue in PD and AD pathologies.

The present disclosure provides chimeric receptor constructs comprising a CD3e extracellular domain and engineered NK and T cells expressing such receptors and methods of making and using same for the treatment of cancer and other diseases of the immune system.

The present invention relates generally to proteins which bind to human epidermal growth factor receptor variant III (EGFRvIII). The present invention also relates to chimeric antigen receptors (CARs) comprising the EGFRvIII binding proteins, nucleic acids and vectors encoding the CARs, as well as cells comprising the CARs. The present invention also relates to methods of treating and diagnosing diseases such as cancer.

Provided herein are novel compositions enriched in gdT cells with high therapeutic potential. Methods to produce such compositions and methods of uses thereof in adoptive immunotherapies are also provided.

Directed evolution using yeast display was employed to isolate novel NKp30 variants that bind to B7H6 with higher affinity compared to the native receptor but retain its fast association and dissociation profile. Two variants, CC3 and CC5, were expressed as soluble Fc-fusion proteins and CARs containing CD28 and CD3? intracellular domains. These Fc fusion protein forms of NKp30 and its variants were better able to bind tumor cells expressing low levels of B7H6 than TZ47, and exhibited improved in vitro tumor cell killing relative to NKp30. Also, CAR T cells expressing the engineered variants produced unique cytokine signatures in response to multiple tumor types expressing B7H6 compared to both NKp30 and TZ47. These findings suggest that natural CAR receptors can be fine-tuned to produce more desirable signaling outputs while maintaining evolutionary advantages in ligand recognition relative to scFvs.

The present disclosure relates to targeted degradation platform technology. For example, the present disclosure relates to bispecific binding agents for degrading endogenous proteins, whether membrane-associated or soluble, using the lysosome pathway. The disclosure also provides methods useful for producing such agents, nucleic acids encoding same, host cells genetically modified with the nucleic acids, as well as methods for modulating an activity of a cell and/or for the treatment of various disorders.

The present disclosure generally relates to, among other things, a new class of receptors engineered to modulate transcriptional regulation in a ligand-dependent manner. In particular, the new receptors contain a heterologous stop-transfer-sequence and a ?-secretase cleavable transmembrane domain. The disclosure also provides compositions and methods useful for producing such receptors, nucleic acids encoding same, host cells genetically modified with the nucleic acids, as well as methods for modulating an activity of a cell and/or for the treatment of various diseases such as cancers.

Embodiments concern methods and/or compositions related to immunotherapy for cancer. In particular embodiments, engager immune cells harbor a vector that encodes a secretable engager molecule. In particular cases, the engager molecule has an activation domain and an antigen recognition domain. In some embodiments, the engager molecules further comprise a cytokine or co-stimulatory domain, for example.

Provided herein is a composition comprising, a cell, comprising nucleic acids encoding a chimeric antigen receptor (CAR) and one or more of signaling proteins selected from K13-vFLIP, MC159-vFLIP, cFLIP-L, cFLIP-p22, HTLV1-Tax and HTLV2-Tax, wherein the CAR comprises an a) extracellular antigen specific domain, b) a transmembrane domain and c) an intracellular signaling domain comprising an immunoreceptor tyrosine-based activation motif (ITAM); wherein c) is located at the C-terminus of the chimeric receptor. In some embodiments, the CAR further comprises one or more co-stimulatory domains. Also provided herein are methods for treating diseases using the compositions described herein.