Disclosed are methods, compositions of matter, and protocols useful for the detection of altered cells in a patient. Immune cells capable of clonal expansion are engineered to produce a soluble signal upon activation and/or clonal expansion. The cells may possess a suicide gene, inducible upon administration pharmacological or light/radiation activatable, so as to eliminate the cells from body when desired. In another embodiment, immune cells produce a localized marker, the marker being visible with imaging technology. In other embodiments cells capable of non-clonal expansion are utilized. The disclosure provides means of utilizing the immunosurveillance properties of immune cells to diagnose and localize diseases associated with alteration of host cells.

Systemic administration of intact, bacterially derived minicells results in rapid accumulation of the minicells in the microenvironment of a brain tumor, in therapeutically significant concentrations, without requiring endothelial endocytosis/transcytosis across the blood brain barrier or any other mechanism by which, pursuant to conventional approaches, nanoparticles have entered into that microenvironment. Accordingly, a wide variety of brain tumors, both primary and metastatic, can be treated by administering systemically a therapeutically effective amount of a composition comprised of a plurality of such minicells, each minicell being a vehicle for an active agent against the tumor, such as a radionuclide, a functional nucleic acid or a plasmid encoding one, or a chemotherapeutic agent.

The present invention relates to an isolated cellular targeted delivery system comprising a CD45+ leukocyte cell comprising within said cell a complex of one or more iron binding proteins and an active pharmaceutically active substance and/or label as well as methods for producing such isolated cellular targeted delivery system and uses of such system for prophylaxis, therapy, diagnosis or theragnosis, in particular for prophylactic or therapeutic vaccination, therapy of cancer, particularly metastatic cancer or inflammatory diseases.

This disclosure provides methods and compositions for detecting Tph cells and/or reducing the number (or frequency) and/or activity of such cells in order to provide therapeutic benefit to a subject having or at risk of developing an autoantibody-associated condition such as an autoantibody-associated autoimmune disease.

Disclosed herein are methods of detecting tumors, monitoring cancer therapy, and selectively inhibiting the proliferation and/or killing of cancer cells utilizing a papilloma pseudovirus or a papilloma virus-like particle (VLP).

A method of producing radiobacteria is provided, especially radiolisteria-.sup.32P. Compositions and methods of use thereof are also provided.

A target tissue can be treated with a radioisotope. Some methods for treating a target tissue with a radioisotope include determining a distance between a target tissue and a surface of a matrix material to be positioned adjacent the target tissue and, based on the determined distance, determining an activity to be mixed with the matrix material to obtain a desired activity concentration. Some methods further include mixing the radioisotope with the matrix material. In some embodiments, the matrix material comprises bone cement, and the target tissue is a tumor in a bone. The radioisotope may be a beta-emitting radioisotope mixed in the cement at a concentration to form a radioactive cement.

A method for loading immunocompetent cells with nanoparticles and/or a cytotoxic substance is for use in the theranostic treatment of patient-specific genetically modified cells. The method includes the steps: (a) providing immunocompetent cells; and (b) loading the immunocompetent cells with the nanoparticles and/or the cytotoxic substance, wherein the nanoparticles and/or the cytotoxic substance are nuclides for radiotherapy. The loading step includes (i) applying the nanoparticles and/or the cytotoxic substance to the immunocompetent cells or mixing the nanoparticles and/or the cytotoxic substance with the immunocompetent cells in a liquid carrier; and (ii) poration of the immunocompetent cells in order to increase the permeability of the cell membranes of the immunocompetent cells for the nanoparticles and/or the cytotoxic substance and thereby loading the immunocompetent cells with the nanoparticles and/or the cytotoxic substance.

A method for porating cells for loading cells with a substance, preferably nuclides for radiotherapy, performs porating in a porating device with cells to be porated in a liquid with the substance. The cell membranes are permeabilized by sonoporation or laser poration in a reactor under real-time-monitoring. Moreover, a device for porating cells, in particular by sonoporation or laser porating, and for loading cells, in particular immunocompetent cells, in particular ?? T cells, includes inlet and outlet openings for a cell solution with cells to be porated and a substance to be taken up by the cells as a load and preferably microbubbles. A poration arrangement extending between the openings has a collector at the inlet opening for collecting cell solution and a reactor in flow connection with the collector. Inside the reactor the cell membranes may be porated and the cells may take up the load.

Disclosed are methods, compositions of matter, and protocols useful for the detection of altered cells in a patient. Immune cells capable of clonal expansion are engineered to produce a soluble signal upon activation and/or clonal expansion. The cells may possess a suicide gene, inducible upon administration pharmacological or light/radiation activatable, so as to eliminate the cells from body when desired. In another embodiment, immune cells produce a localized marker, the marker being visible with imaging technology. In other embodiments cells capable of non-clonal expansion are utilized. The disclosure provides means of utilizing the immunosurveillance properties of immune cells to diagnose and localize diseases associated with alteration of host cells.