METHODS FOR DETECTING AND REVERSING IMMUNE THERAPY RESISTANCE

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 cd38pd-1 t cells, cd38cd8 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.

Inventor(s): Samir N. Khleif, Vivek Verma, Seema Gupta

CPC Classification: A61K39/39558 (PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES (devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms ; chemical aspects of, or use of materials for deodorisation of air, for disinfection or sterilisation, or for bandages, dressings, absorbent pads or surgical articles ; soap compositions ))

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