Checkpoint blockade and microsatellite instability
AssigneeThe Johns Hopkins University
InventorsLuis Diaz, Bert Vogelstein, Kenneth W. Kinzler, Nickolas Papadopoulos, Dung Le, Drew M. Pardoll, Suzanne L. Topalian
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Abstract
Blockade of immune checkpoints such as cytotoxic T-lymphocyte antigen-4 (CTLA-4) and programmed death-1 (PD-1) shows promise in patients with cancer. Inhibitory antibodies directed at these receptors have been shown to break immune tolerance and promote anti-tumor immunity. These agents work particularly well in patients with a certain category of tumor. Such tumors may be particularly susceptible to treatment because of the multitude of neoantigens which they produce.
Claims28
A method for treating a patient having a solid tumor selected from the group consisting of:
- endometrial cancer, small bowel cancer, gastric cancer, ampullary cancer, cholangiocarcinoma, pancreatic cancer, prostate cancer, breast cancer, esophageal cancer, liver cancer, ovarian cancer, uterine cancer, cervical cancer, bladder cancer, testicular cancer and oral cancer, the method comprising:
- in response to determining that the solid tumor is microsatellite instability high or DNA mismatch repair deficient, treating a patient having a solid tumor selected from the group consisting of:
- endometrial cancer, small bowel cancer, gastric cancer, ampullary cancer, cholangiocarcinoma, pancreatic cancer, prostate cancer, breast cancer, esophageal cancer, liver cancer, ovarian cancer, uterine cancer, cervical cancer, bladder cancer, testicular cancer and oral cancer with a therapeutically effective amount of pembrolizumab based on a determination that the solid tumor has progressed following at least one prior cancer treatment, and further based on previous testing of a biological sample obtained from the patient that the patient's solid tumor exhibits at least one marker for high microsatellite instability or DNA mismatch repair deficiency.
A method for reducing the risk ofprogression of a solid tumor selected from the group consisting of:
- endometrial cancer, small bowel cancer, gastric cancer, ampullary cancer, cholangiocarcinoma, pancreatic cancer, prostate cancer, breast cancer, esophageal cancer, liver cancer, ovarian cancer, uterine cancer, cervical cancer, bladder cancer, testicular cancer and oral cancer that has progressed following at least one prior treatment in a patient, the method comprising:
- in response to determining that the solid tumor is microsatellite instability high or DNA mismatch repair deficient, treating the patient with a therapeutically effective amount of pembrolizumab based on previous testing of a biological sample obtained from the patient that the patient's solid tumor exhibits at least one marker for high microsatellite instability or DNA mismatch repair deficiency.
Dependencies are inferred from the claim text.