Abstract: Compositions and methods of their use to detect and treat anti-PD1 therapy resistance are provided herein. Compositions that immunospecifically bind and deplete dysfunctional T cells are provided. The dysfunctional T cells that are depleted include CD38+PD-1+ T cells, CD38+CD8+ T-cells, or both. The dysfunctional T cells can be depleted, for example, by administering an antibody or fusion protein that specifically binds to dysfunctional T cells and promotes their depletion. In one embodiment the antibody is a bispecific antibody that can be specific for CD38 and CD8, or it can be specific for CD38 and PD-1. Also disclosed is a method of detecting and treating anti-PD1 therapy resistance by measuring the amount of CD38+PD1+CD8 T cells in blood or tissue samples obtained from a subject prior to anti-PD1 therapy and administering an anti-CD38/CD8 or anti-CD38/PD-1 depleting/blocking antibody to the subject prior to anti-PD1 therapy.

Abstract: Compositions and methods of their use to detect and treat anti-PD1 therapy resistance are provided herein. Compositions that immunospecifically bind and deplete dysfunctional T cells are provided. The dysfunctional T cells that are depleted include CD38+PD-1+ T cells, CD38+CD8+ T-cells, or both. The dysfunctional T cells can be depleted, for example, by administering an antibody or fusion protein that specifically binds to dysfunctional T cells and promotes their depletion. In one embodiment the antibody is a bispecific antibody that can be specific for CD38 and CD8, or it can be specific for CD38 and PD-1. Also disclosed is a method of detecting and treating anti-PD1 therapy resistance by measuring the amount of CD38+PD1+CD8 T cells in blood or tissue samples obtained from a subject prior to anti-PD1 therapy and administering an anti-CD38/CD8 or anti-CD38/PD-1 depleting/blocking antibody to the subject prior to anti-PD1 therapy.

Abstract: The present invention provides for a biocompatible drug delivery device for the targeted treatment of cancer that is implantable within the tumorous mass of a patient. In one embodiment, the device comprises two polarizable elements mechanically coupled by a connecting element. The device also comprises one or more cancer treatment agents. When the polarizable elements are depolarized, such as by the application of ionizing radiation, the two polarizable elements are repelled from each other and release the cancer treatment agent. In another embodiment, one or more treatment agents are expelled from a miniaturized syringe when internal pressure of the device is increased by the production of gas bubbles in response to the application of ionizing radiation.

Abstract: A microfluidic chip and compatible bio-sensor are provided to detect and/or quantify an analyte in a sample fluid, and preferably to simultaneously quantify multiple analyte(s) in a sample fluid volume. A fluid volume containing microbeads is flowed through an elongate planar sample chamber of the microfluidic chip. Microbead traps or barriers in the sample chamber retain the microbeads. The sample fluid volume is Excitation flowed through the sample chamber. A conjugate specific to the analyte is and labeled with a fluorophore is introduced into the sample chamber. In the biosensor, an excitation wavelength is directed parallel to the plane of the sample chamber. Any fluorescent emissions from the sample chamber are detected in a direction substantially orthogonal to the plane of the sample chamber by a photodetector, and correlated to an amount or concentration length of sample chamber of analyte in the sample fluid volume.

Abstract: The invention is directed to a method for detecting analytes, particularly vitamins, using a lateral flow immunoassay. The method may be used to detect vitamin D, particularly 25-hydroxy vitamin D3 or 1,25-dihydroxy vitamin D3. The method involves obtaining a fluid sample from a subject; applying the sample to a lateral flow test strip comprising a conjugate pad capable of releasing a labelled antibody against vitamin D, and a detection membrane comprising a first capture reagent specific to the antibody and immobilized on a test band; and detecting the presence or absence of vitamin D in the sample. The presence of a detectable signal in the test band is indicative of vitamin D deficiency.