Provided herein are methods of treating cancer by activating resident memory T cells using one or more antigenic peptides.

Disclosed herein are methods of increasing numbers of monocytes to a tumor or cancer metastasis site in a subject. Non-limiting embodiments include administering or using a Nur77 polypeptide or subsequence thereof; a Nur77 agonist; a CX3CR1 agonist; CD14+ CD16.sup.+ monocytes and/or CD14dimCD16.sup.+(CD115.sup.+CD11b.sub.+GR1.sup.?(Ly6C?)) monocytes; CD14.sup.+CD16.sup.+ monocytes and/or CD14dimCD16.sup.+(CD115.sup.+CD11b.sup.+GR1.sup.?(Ly6C?)) monocytes contacted with a Nur77 agonist or contacted with a CX3CR1 agonist. Also disclosed herein are methods of increasing, stimulating, activating or promoting monocyte migration to or mobilization against a tumor or cancer metastasis in a subject. Non-limiting embodiments include administering a Nur77 polypeptide or sub-sequence thereof; a Nur77 agonist; a CX3CR1 agonist; CD14+ CD16+ monocytes and/or CD14dimCD16.sup.+(CD115.sup.+CD11b.sup.+GR1.sup.? (Ly6C?)) monocytes; or CD14.sup.+CD16.sup.+ monocytes and/or CD14dimCD16.sup.+(CD115.sup.+CD11b.sup.+GR1.sup.?(Ly6C?)) monocytes contacted with a Nur77 agonist or contacted with a CX3CR1 agonist.

Immunomodulating polynucleotides are disclosed. The immunomodulating polynucleotides may contain 5-modified uridine, 5-modified cytidine, a total of from 6 to 16 nucleotides, and/or one or more abasic spacers and/or internucleoside phosphotriesters. Also disclosed are conjugates containing a targeting moiety and one or more immunomodulating polynucleotides. The immunomodulating polynucleotides and conjugates may further contain one or more auxiliary moieties. Also disclosed are compositions containing the immunomodulating polynucleotides or the conjugates containing one or more stereochemically enriched internucleoside phosphorothioates. Further disclosed are pharmaceutical compositions containing the immunomodulating polynucleotides or the conjugates and methods of their use.

The present invention relates to therapeutic and prophylactic methods based on inhibition of CIS in NK cells. In particular, the present invention relates to treating or preventing a NK-responsive condition by administering to a subject a CIS inhibitor, or administering CIS-inhibited NK cells. The invention further relates to methods for identifying a CIS inhibitor, and for determining a likelihood of cancer response to treatment with CIS inhibition.

In certain embodiments, this disclosure relates to conjugates comprising a polypeptide of GM-CSF and a polypeptide IL-4. Typically, the GM-CSF and IL-4 are connected by a linker, e.g., polypeptide. In certain embodiments, the disclosure relates to isolated nucleic acids encoding these polypeptide conjugates, vectors comprising nucleic acid encoding polypeptide conjugates, and protein expression systems comprising these vectors such as infectious viral particles and host cells comprising such nucleic acids.

Provided herein are methods and compositions useful for treating cancer, such as prostate cancer, through adoptive cell transfer of T cells derived from patients and genetically engineered to express MDA-7/IL-24 and/or other immune modulating agents. The methods described herein result in cancer cell death and reprogramming of the tumor immune compartment to restore antitumor immunity both at a primary tumor site and systemically.

Novel costimulatory fusion proteins and DNA sequences that enhance T cell responses to weakly immunogenic and/or lowly expressed antigens and that confer T cell resistance against MDSC-mediated suppression are disclosed. The fusion proteins comprise portions of CD4, CD8? or the T cell receptor linked to a specific region of MyD88 or other signaling molecules. These fusion proteins and sequence variants thereof improve T cell activation and responsiveness. Also disclosed is the use of these molecules in host cells as a means to enhance and costimulate responses of immune cells including cytotoxic CD8.sup.+ T cells and the use of these cells to treat cancer, infectious agents and other diseases.

The present invention relates to Chimeric Antigen Receptors (CARs) comprising antigen binding domains that specifically bind melanoma cells, polynucleotides encoding such CARs, and vectors comprising such polynucleotides. The present invention further relates to engineered cells comprising such polynucleotides and/or transduced with such viral vectors, and compositions including a plurality of engineered T cells. The present invention also relates to methods for manufacturing such engineered T cells and compositions and uses in treating a melanoma such engineered T cells and compositions.

A novel chimeric receptor composition, a recombinant vector, a cell, and an application thereof. The novel chimeric receptor composition includes a conventional chimeric antigen receptor (CAR), and a NKG2D chimeric receptor including a full-length sequence or a truncated fragment of NKG2D, DAP10, and/or DAP12, referred to as a SNR-armed CAR. The chimeric receptor composition enables a conventional CAR-T cell to express a NKG2D extracellular domain and an intracellular signal domain, expands a CAR-T antigen recognition spectrum, solves the tumor heterogeneity, achieves a lower level of cytokine release while enhancing the killing capability of CAR-T on tumor cells expressing target antigens, reduces the possibility of cytokine storm occurrence, and improves the CAR-T security.

The subject matter described herein is directed to methods for determining the potency of isolated and expanded tumor infiltrating lymphocytes (TILs) and producing therapeutic populations of TILs, and compositions involving the same and methods of treatment involving the same.