Profiling peptides and methods for sensitivity profiling
View Patent ↗The present disclosure is generally directed to profiling peptides, compositions, and kits, as well as methods of use thereof. The profiling peptides comprise an Mcl-1 binding domain, and optionally a cellular uptake moiety. The methods of using such profiling peptides include predicting sensitivity of a cancer, selecting a treatment, treating a cancer, producing a sensitivity profile, and the like.
1. A method for treating a subject with an MCL-1 dependent hematological cancer comprising:
acquiring bone marrow cells from the subject;
profiling a plurality of bone marrow cells with a profiling peptide comprising SEQ ID NO: 14;
determining a Mcl-1 dependency percentage (MDP) of the subject; and
administering alvocidib to a subject with an MDP determined to be at least 40%.
2. The method of claim 1 wherein the hematologic cancer is multiple myeloma, myelodysplastic syndrome (MDS), or acute myeloid leukemia (AML).
3. The method of claim 1 wherein the cancer is AML.
4. The method of claim 1 wherein the cancer is MDS.
5. The method of claim 1 wherein the cancer is multiple myeloma.
6. The method of claim 1 wherein cytarabine and mitoxantrone are also administered to the subject.
7. The method of claim 1 wherein the profiling is performed in the absence of a permeabilizing agent.
8. A method for treating a subject with an MCL-1 dependent hematological cancer selected from acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) comprising:
acquiring bone marrow cells from the subject;
profiling a plurality of bone marrow cells with a profiling peptide comprising SEQ ID NO: 14;
determining a Mcl-1 dependency percentage (MDP) of the subject; and
administering alvocidib to a subject with an MDP determined to be at least 40%.
9. The method of claim 8 wherein the hematological cancer is AML.
10. The method of claim 8 wherein the hematological cancer is MDS.
11. The method of claim 8 wherein the profiling is performed in the absence of a permeabilizing agent.
12. A method for treating a subject having acute myeloid leukemia (AML) comprising:
acquiring bone marrow cells from the subject;
profiling a plurality of bone marrow cells with a profiling peptide comprising SEQ ID NO: 14 wherein the profiling is performed in the absence of a permeabilizing agent;
determining a MCL-1 dependency percentage (MDP) of the subject; and
administering alvocidib to a subject with an MDP determined to be at least 40%.
13. A method for treating a subject having myelodysplastic syndrome (MDS) comprising:
acquiring bone marrow cells from the subject;
profiling a plurality of bone marrow cells with a profiling peptide comprising SEQ ID NO: 14 wherein the profiling is performed in the absence of a permeabilizing agent;
determining a MCL-1 dependency percentage (MDP) of the subject; and
administering alvocidib to a subject with an MDP determined to be at least 40%.