Compositions comprising and methods for the treatment of cancer using a neoTCR based cell therapy with a CD8 expression construct.

The present disclosure provides novel cell compositions engineered to express at least a chimeric antigen receptor and a survival factor. Methods of using such cell compositions are also described.

Activity-inducible fusion proteins including a transcription factor and a heat-shock protein 90 (hsp90) binding domain are described. The activity of the transcription factor is regulated utilizing a drug molecule that binds the hsp90 binding domain. In the absence of the drug molecule, the transcription factor is in an inactive state but can be activated in the presence of the drug molecule. The activity-inducible transcription factors can be used to alter the activation state of immune cells, and optionally can be co-expressed with a chimeric antigen receptor (CAR).

Modified T cells comprising ectopic CD40 proteins (such as chimeric CD40 proteins including a CD40 extracellular domain and a heterologous intracellular domain) are provided. Also provided are compositions, including pharmaceutical formulations, comprising the modified T cells, and methods for increasing T cell-mediated tumor cell-specific cytotoxicity using the same. Methods of treating a subject with cancer including administering to the subject the modified T cells, thereby activating an innate immune response and/or an adaptive immune response in the subject are also provided.

Provided are methods for activating an antigen-presenting cell and eliciting an immune response by inducing an inducible pattern recognition receptor adapter, or adapter fragment, and CD40 activity. Also provided are nucleic acid compositions comprising sequences coding for chimeric proteins that include an inducible CD40 peptide and an inducible pattern recognition receptor adapter or adapter fragment.

Provided in some aspects are epigenetic-modifying DNA-targeting systems, such as CRISPR-Cas/guide RNA systems, that bind to or target a target site in a gene or regulatory element thereof in a T cell. In some aspects, the provided epigenetic modifying DNA-targeting systems provided herein modulate a T cell phenotype or activity. In particular, the provided embodiments relate to the transcriptional activation of genes that promote a stem cell-like memory T (T.sub.SCM) cell phenotype. In some aspects, also provided are compositions, polynucleotides, vectors, cells, and pluralities and combinations thereof, and methods and uses related to the provided epigenetic-modifying DNA-targeting systems, for example in modulating the phenotype in T cells including in connection with adoptive T cell therapy.

Provided in some aspects are epigenetic-modifying DNA-targeting systems, such as CRISPR-Cas/guide RNA systems, that bind to or target a target site in a gene or regulatory element thereof in a T cell. In some aspects, the provided epigenetic modifying DNA-targeting systems provided herein modulate a T cell phenotype or activity. In particular, the provided embodiments relate to the transcriptional activation of genes that promote a stem cell-like memory T (T.sub.SCM) cell phenotype. In some aspects, also provided are compositions, polynucleotides, vectors, cells, and pluralities and combinations thereof, and methods and uses related to the provided epigenetic-modifying DNA-targeting systems, for example in modulating the phenotype in T cells including in connection with adoptive T cell therapy.

Methods for inducing a sustained immune response against phosphorylated Tau in humans are described. The methods include administering to the subject an effective amount of liposomes including a toll-like receptor 4 agonist, a helper T-cell epitope, a lipidated CpG oligonucleotide, and a Tau phosphopeptide presented on the surface of the liposome to thereby obtain the sustained immune response.

Methods for inducing a sustained immune response against phosphorylated Tau in humans are described. The methods include administering to the subject an effective amount of liposomes including a toll-like receptor 4 agonist, a helper T-cell epitope, a lipidated CpG oligonucleotide, and a Tau phosphopeptide presented on the surface of the liposome to thereby obtain the sustained immune response.

Recombinant proteins that stimulate an immune response in the presence of naturally inhibitory ligand binding are described. The recombinant proteins include an extracellular domain of an inhibitory immune cell protein and an intracellular domain of a stimulatory immune cell protein connected via a transmembrane domain. The recombinant proteins can be used to stimulate immune cell activation in the fight against cancers and infectious diseases, among other uses.