Abstract: Oncolytic viruses encoding a recombinant form of TGF-? engineered to prevent homodimerization and recruitment of TGF-? receptor I are described. The engineered TGF-? monomers function as dominant-negative TGF-? inhibitors. Oncolytic viruses encoding a TGF-? monomer can be used for cancer immunotherapy to inhibit the immunosuppressive tumor microenvironment.

Abstract: Provided are improved methods for making immune effector cells, as well as improved immune effector cells generated using the methods. The improved T cells have improved respiratory capacity and mitochondrial mass. Adoptive T cell immunotherapies using such cells demonstrate improved survival, expansion, and persistence in vivo.

Abstract: Recombinant oncolytic viruses (OVs) that express one or more metabolic modulator proteins, such as an adipokine (e.g., leptin or chemerin), insulin, and/or IGF-1, and methods of their use to treat cancer, for example in immunotherapy anti-cancer treatments. In some examples, such recombinant OVs and methods increase T cell infiltration into the tumor or tumor microenvironment.

Abstract: The present disclosure provides recombinant T cells that include a vector encoding one or more of peroxisome proliferator-activated receptor (PPAR) gamma coactivator 1-alpha (PGC1?), mitochondrial transcription factor A (Tfam), GA binding protein transcription factor alpha subunit (GABPA), and estrogen-related receptor alpha (ERR?). Such recombinant T cells can also include a chimeric antigen receptor (CAR) or a recombinant T cell receptor (TCR). Methods of using these recombinant T cells in cancer immunotherapy are provided. Also provided are kits and compositions that can be used with such methods.

Abstract: Recombinant oncolytic viruses (OVs) that express one or more metabolic modulator proteins, such as an adipokine (e.g., leptin or chemerin), insulin, and/or IGF-1, and methods of their use to treat cancer, for example in immunotherapy anti-cancer treatments. In some examples, such recombinant OVs and methods increase T cell infiltration into the tumor or tumor microenvironment.

Abstract: The invention is directed to treatment of cancer, infections and various inflammatory and autoimmune conditions by affecting regulatory T cell stability and function via a Neuropilin-1:Semaphorin axis.

Abstract: The present disclosure provides recombinant T cells that include a vector encoding one or more of peroxisome proliferator-activated receptor (PPAR) gamma coactivator 1-alpha (PGC1?), mitochondrial transcription factor A (Tfam), GA binding protein transcription factor alpha subunit (GABPA), and estrogen-related receptor alpha (ERR? ). Such recombinant T cells can also include a chimeric antigen receptor (CAR) or a recombinant T cell receptor (TCR). Methods of using these recombinant T cells in cancer immunotherapy are provided. Also provided are kits and compositions that can be used with such methods.

Abstract: The present disclosure provides methods for expanding tumor-infiltrating lymphocytes (TILs), such as tumor-infiltrating T cells, utilizing an agonist of PGC1? in vivo, ex vivo, or both. Exhausted T cells present in the TIL population fail to effectively proliferate, produce cytokines, or kill target cells. The present disclosure provides methods to correct these defects through the use of pharmacologic agents to reprogram the metabolism of the exhausted intratumoral T cells. Exemplary agonists of PGC1? include proliferator-activated receptor (PPAR)-gamma agonists (e.g., a thiazolidinedione (TZD), aleglitazar, farglitazar, muraglitazar, or tesaglitazar), AMPK activators (e.g., 5-aminoimidazole-4-carboxamide ribonucleotide, AICAR), and sirtuin activators (e.g., resveratrol, SRT1720, SRT2104, SRT2183, SRT1460). Also provided are kits can compositions that can be used with such methods.

Abstract: The invention is directed to treatment of cancer, infections and various inflammatory and autoimmune conditions by affecting regulatory T cell stability and function via a Neuropilin-1:Semaphorin axis.

Abstract: The invention is directed to treatment of cancer, infections and various inflammatory and autoimmune conditions by affecting regulatory T cell stability and function via a Neuropilin-1:Semaphorin axis. The present invention satisfies this and other needs by demonstrating that the regulatory T cell (Treg)-restricted neuropilin-1 (Nrp 1) interacts with the cell surface ligand semaphorin-4a (Sema4a) (e.g., on conventional T cells (Tconv), conventional dendritic cells (cDCs), and/or plasmacytoid dendritic cells (pDCs)) to potentiate reg function and enhance their survival at inflammatory sites.

Abstract: The invention is directed to treatment of cancer, infections and various inflammatory and autoimmune conditions by affecting regulatory T cell stability and function via a Neuropilin-1:Semaphorin axis. The present invention satisfies this and other needs by demonstrating that the regulatory T cell (Treg)-restricted neuropilin-1 (Nrp 1) interacts with the cell surface ligand semaphorin-4a (Sema4a) (e.g., on conventional T cells (Tconv), conventional dendritic cells (cDCs), and/or plasmacytoid dendritic cells (pDCs)) to potentiate reg function and enhance their survival at inflammatory sites.