PD1+CD38+ CD8 T-cells, a marker for anti-PD1 therapy resistance and selection marker for treatment or continuation of treatment of patients, and a target to reverse resistance

PD1+CD38+ CD8 T-cells, a marker for anti-PD1 therapy resistance and selection marker for treatment or continuation of treatment of patients, and a target to reverse resistance
 
Current state of the art
A number of new checkpoint inhibitors are used in cancer therapy. PD-1 inhibitors such as Pembrolizumab (Keytruda), Nivolumab (Opdivo), and Cemiplimab (Libtayo), and PDL-1 inhibitors such as Atezolizumab (Tecentriq), Avelumab (Bavencio),and Durvalumab (Imfinzi) are used to treat cancers such as melanoma of the skin, non-small cell lung cancer, kidney cancer, bladder cancer, head and neck cancers, Merkel cell carcinoma, and Hodgkin lymphoma.
 
Problems with current state of art
Although checkpoint inhibitors have shown significant clinical response, they are effective in only 10-50% of patients. We must find ways to improve the therapeutic outcome. 
 
Advantages of our invention
This invention teaches the enhanced depletion of dysfunctional T-cells, CD38+PD-1+ or CD38+CD8+, or both. The dysfunctional T-cells are depleted by administering an antibody that specifically binds to the dysfunctional T-cells and promotes their removal. The remaining T-cells are then primed with a vaccine while, or after which, a checkpoint inhibitor is administered.
 
AURI: #2018-032

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