Lung-cancer specific t cell dysfunction
AssigneeMassachusetts Institute of Technology
InventorsKarl Dane Wittrup, J. Christopher Love, Stefani Spranger, Brendan Horton, Duncan Morgan
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Abstract
Methods for identifying patients susceptible to treatment with checkpoint inhibitors are provided herein. Also provided are reagents for analyzing T cell responses for understanding resistance to checkpoint inhibitor therapy and understanding therapeutics for overcoming that resistance. Therapeutic strategies, for instance, for treating cancer, are also provided.
Claims26
A method for identifying a T cell having a dysfunctional property, comprising isolating a T cell and determining the presence of effector molecules associated with the T cell, wherein when the T cell expresses high levels of CD49d and CCL5, and TOX in the absence of TIM3 the T cell is a dysfunctional CD8+ T (Tdys) cell.
A composition comprising an isolated population of dysfunctional CD8+ T (Tdys) cells, wherein the T cells express high levels of CD49d and CCL5 and TOX in the absence of TIM3 and are not associated with or have low levels of effector molecules CD25, GzmB and IFN-γ.
A method for treating a subject having cancer, comprising
- isolating a sample containing T cells from the subject, determining whether the sample contains dysfunctional CD8+ T (Tdys) cells, wherein if the sample contains Tdys cells then the subject is treated with a checkpoint based enhancing therapy and wherein if the sample does not contain Tdys cells then the subject is treated with a checkpoint based therapy (CBT).
A method for treating a subject having cancer, comprising
- administering to the subject a checkpoint based enhancing therapy, wherein the checkpoint based enhancing therapy is a compound that disrupts the activity of Tdys cells and administering to the subject a checkpoint based therapy (CBT) in an effective amount to treat the cancer.
A tumor cell stably expressing cerulean-SIY.
Dependencies are inferred from the claim text.