Provided are anti-GCC single domain antibodies (e.g., VHH domain antibodies), and chimeric antigen receptors (CARs) that bind to GCC comprising same in an extracellular antigen binding domain, a transmembrane domain, and an intracellular signaling domain. Immune cells transduced with the disclosed CAR constructs and/or a chimeric receptor can be used for cancer immunotherapy.

Provided herein are compositions and methods for adoptive cell therapy comprising engineered immune cells that express a tumor antigen-targeted chimeric antigen receptor and a prodrug converting enzyme.

A versatile carrier system for systemic delivery of oncolytic viruses comprises dendritic cells having at least one oncolytic virus loaded therein. It is believed that the dendritic cells will protect the oncolytic virus(es) against neutralizing antibodies, can transport the oncolytic virus(es) to targeted tumor locations, and then deliver virions to the tumor locations.

Therapeutic modalities are provided for targeting adoptive cellular therapies to specific sites of disease, involving the use of specific repertoirs of PRR ligands. In effect, innate immune system signaling is provoked so as to facilitate the homing of adoptive immune cells to sites of disease, for example to the site of a solid tumor.

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.

Provided herein are compositions and methods for adoptive cell therapy comprising engineered immune cells that express a tumor antigen-targeted chimeric antigen receptor and a prodrug converting enzyme.