The present disclosure provides methods and compositions for enhancing the immune response toward cancers and pathogens. It relates to immunoresponsive cells comprising antigen recognizing receptors (e.g., chimeric antigen receptors (CARs) or T cell receptors (TCRs)), and expressing increased level of IL-18. In certain embodiments, the engineered immunoresponsive cells are antigen-directed and resistant to immunosuppression and/or have enhanced immune-activating properties.

The present invention relates to the field of bioengineering, and in particular to a chimeric antigen receptor (CAR) expression vector and use thereof. The CAR expression vector comprising a polynucleotide encoding a CAR and full length or fragment of a polynucleotide encoding a granulocyte-macrophage colony-stimulating factor (GM-CSF). The CAR-GM-T cell constructed by the present invention is capable of expressing high-level GM-CSF, not only directly enhancing killing activity of the CAR-GM-T cell per se but also facilitating the infiltration of the CAR-GM-T cell into a solid tumor. The CAR-GM-T cell has a stronger immune modulation function compared to the conventional CAR-T cell and systematically triggers the endogenous anti-tumor immune response, thereby achieving superior therapeutic efficacy against a solid tumor.

The present disclosure relates to IL2 agonists with improved therapeutic profiles.

The present invention provides methods for expanding TILs and producing therapeutic populations of TILs. According to exemplary embodiments, at least a portion of the therapeutic population of TILs are gene-edited to enhance their therapeutic effect. According to further embodiments, methods for gene-editing TILs include intratumoral delivery of expression vectors for immune checkpoint inhibitors using an electroporation system prior to harvesting the tumor for TIL production. According to yet further embodiments, an adjuvant therapy for cancer includes delivery of expression vectors for immune checkpoint inhibitors before, after or before and after infusion of TILs for treating cancer.

The present disclosure provides orthogonal chimeric cytokine receptor/orthogonal cytokine pairs and compositions and methods for modified immune cells or precursors thereof (e.g., modified T cells) comprising an orthogonal chimeric cytokine receptor (e.g., an oIL2R-IL9R chimeric receptor) and a chimeric antigen receptor (CAR) or a T cell receptor (TCR). The present disclosure further provides an oncolytic adenoviral vector comprising a nucleic acid sequence encoding an orthogonal cytokine (e.g., oIL2), as well as methods of using the modified cells and the vector for treating cancer in a subject in need thereof.

The disclosure features amphiphilic ligand conjugates including a peptide or a ligand for a mucosal-associated invariant T-cell and a lipid and T cell receptor modified immune cells. The disclosure also features compositions and methods of using the same, for example, to stimulate proliferation of T cell receptor expressing cells.

The present invention provides improved and/or shortened processes and methods for preparing TILs in order to prepare therapeutic populations of TILs with increased therapeutic efficacy for the treatment of cancer with TILs in combination with CT-LA-4 and PD-1 inhibitors and/or PD-L1 inhibitors as described herein.

Disclosed herein are chimeric antigen receptor (CAR) polypeptides that can be used with adoptive cell transfer to target and kill IL13Ra2-expressing cancers. Also disclosed are immune effector cells, such as T cells or Natural Killer (NK) cells, that are engineered to express these CARs. Therefore, also disclosed are methods of providing an anti-tumor immunity in a subject with an IL13Ra2-expressing cancer that involves adoptive transfer of the disclosed immune effector cells engineered to express the disclosed CARs.

The invention provides a chimeric antigen receptor (CAR) having antigenic specificity for CD70, the CAR comprising: an antigen binding-transmembrane domain comprising a CD27 amino acid sequence lacking all or a portion of the CD27 intracellular T cell signaling domain; a 4-1BB intracellular T cell signaling domain; a CD3? intracellular T cell signaling domain; and optionally, a CD28 intracellular T cell signaling domain. Nucleic acids, recombinant expression vectors, host cells, populations of cells, and pharmaceutical compositions relating to the CARs are disclosed. Methods of detecting the presence of cancer in a mammal and methods of treating or preventing cancer in a mammal are also disclosed.

Compounds, compositions, and methods for use in inhibiting the E3 enzyme Cbl-b in the ubiquitin proteasome pathway are disclosed. The compounds, compositions, and methods can be used to modulate the immune system, to treat diseases amenable to immune system modulation, and for treatment of cells in vivo, in vitro, or ex vivo. Also disclosed are pharmaceutical compositions comprising a Cbl-b inhibitor and a cancer vaccine, as well as methods for treating cancer using a Cbl-b inhibitor and a cancer vaccine; and pharmaceutical compositions comprising a Cbl-b inhibitor and an oncolytic virus, as well as methods for treating cancer using a Cbl-b inhibitor and an oncolytic virus.