Technology provided herein relates to methods of treating cancer comprising administering to a subject in need thereof a first stem cell (SC) modified to release an oncolytic virus and a second SC which is gene edited to inactivate a receptor for the oncolytic virus, thereby generating a stem cell resistant to the virus, wherein the second SC is also engineered to express an immunomodulatory polypeptide agent. Compositions comprising a first and second SC, and uses thereof, are also provided herein.

The invention concerns APCs, such as DCs, comprising a combination of an exogenous type I interferon and an exogenous CD40-L or one or more heterologous nucleic acid sequences encoding a combination of an exogenous type I IFN and an exogenous CD40-L, such as a combination of IFN and CD40-L; and methods for treating a malignancy by administering such APCs to a subject in need thereof. In certain embodiments, a subject is treated with an irradiation therapy before administering the APCs, such as DCs, of the invention. The invention also concerns an oncolytic virus comprising a combination of a type I IFN and CD40-L or one or more nucleic acid sequences encoding a combination of a type I IFN and CD40-L, such as a combination of IFN and CD40-L; and methods for treating a malignancy by administering such oncolytic virus to a subject in need thereof.

Provided herein are chimeric priming receptors that bind PSMA and chimeric antigen receptors that bind CA9. Also provided are systems of chimeric priming receptors that bind PSMA and chimeric antigen receptors that bind CA9, cells expressing such systems, and methods of use thereof.

This disclosure relates to leukocyte compositions that comprise immune cells that are modified for enhanced in vivo anti-tumor activity. The leukocyte compositions are enriched for CD4+ Th1 cells or other differentiated states and optionally depleted of CD8+ T cells.

Methods and compositions are provided herein whereby a patient with cancer is administered a treatment comprising NK cells in order to induce expression of MHC-I in a tumor, and wherein subsequent treatment with T cells effectively targets tumor associated antigens and neoepitopes presented by newly expressed MHC-I in said tumor cells.