Systems and methods for histotripsy immunosensitization

Abstract

Systems and methods for histotripsy and immunotherapy are provided. In some embodiments, histotripsy can be applied to a target tissue volume to lyse and solubilize the target tissue volume to release tumor antigens. In some embodiments, an immune response of the treatment can be evaluated. In other embodiments, an immune therapy can be applied after applying the histotripsy. In one embodiment, the lysed and solubilized cells can be extracted from the tissue. The extracted cells can be used to create immune therapies, including vaccines.

What is claimed is: 
     
         1 . A histotripsy therapy system, comprising:
 a medical imaging modality configured to identify at least one target tumor;   a histotripsy therapy transducer array;   a robotic positioning system coupled to the histotripsy therapy transducer array, the robotic positioning system being configured to place a focus of the histotripsy transducer array within the at least one target tumor; and   an electronic controller configured to determine a treatment volume and a treatment location of the at least one target tumor that will increase a cell response of releasing tumor antigens, the electronic controller being further configured to control application of histotripsy treatment with the histotripsy therapy transducer array based on the treatment volume and the treatment location to the at least one target tumor to mechanically lyse and solubilize tumor cells to release the tumor antigens.   
     
     
         2 . The system of  claim 1 , further comprising an evaluation device configured to evaluate an immune response of the lysed and solubilized tumor cells. 
     
     
         3 . The system of  claim 1 , wherein the cell response includes immunogenic cell death, infiltration of inflammatory and antigen presenting cells, infiltration and activation of T cells, increased tumor-specific T cells, infiltration of natural killer cells, B cells and CD4+ T cells, and/or depletion of immunosuppressive regulatory T cells and myeloid-derived suppressor cells. 
     
     
         4 . The system of  claim 1 , wherein the treatment volume of the at least one target tumor ranges from 25% to 90% of a volume of the at least one target tumor. 
     
     
         5 . The system of  claim 4 , wherein the treatment volume of the at least one target tumor is at least 1 cm 3  in volume. 
     
     
         6 . The system of  claim 2 , wherein the evaluation device is configured to provide an assessment of immunological cell death and/or immune activation. 
     
     
         7 . The system of  claim 2 , wherein the evaluation device comprises a tissue biopsy device. 
     
     
         8 . The system of  claim 1 , wherein the medical imaging modality comprises CT, MRI, and/or PET imaging. 
     
     
         9 . The system of  claim 1 , wherein the system is configured to elicit an immune response in at least one distant tumor of the same phenotype as the at least one target tumor. 
     
     
         10 . The system of  claim 9 , wherein the at least one distant tumor is located in a different organ or anatomical location than the at least one target tumor. 
     
     
         11 . The system of  claim 1 , wherein the at least one target tumor is located in the group consisting of a liver, a kidney, a spleen, a pancreas, a colorectal, a bowel, a stomach, an esophagus, a breast, a lung, a head, a neck, a thyroid, skin, nervous tissue, hematological malignancies, a sarcoma, primary and metastatic lesions, and brain tissue. 
     
     
         12 . The system of  claim 1 , wherein the treatment location comprises only a central portion of the at least one target tumor. 
     
     
         13 . The system of  claim 1 , wherein the treatment location comprises only a periphery of the at least one target tumor. 
     
     
         14 . The system of  claim 1 , wherein the treatment location comprises a plurality of programmed treatment locations distributed spatially through the at least one target tumor.