Profiling peptides and methods for sensitivity profiling
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 a plurality of bone marrow cells from the subject;
profiling the 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 15%.
2. The method of claim 1 wherein the subject administered alvocidib has an MDP determined to be at least 20%.
3. The method of claim 1 wherein the subject administered alvocidib has an MDP determined to be at least 25%.
4. The method of claim 1 wherein the subject administered alvocidib has an MDP determined to be at least 30%.
5. The method of claim 1 wherein the subject administered alvocidib has an MDP determined to be at least 35%.
6. The method of claim 1 wherein the hematological cancer is multiple myeloma, myelodysplastic syndrome (MDS), or acute myeloid leukemia (AML).
7. The method of claim 1 wherein the hematological cancer is AML.
8. The method of claim 1 wherein the hematological cancer is MDS.
9. The method of claim 1 wherein the hematological cancer is multiple myeloma.
10. The method of claim 1 wherein cytarabine and mitoxantrone are also administered to the subject.
11. The method of claim 1 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 a plurality of bone marrow cells from the subject;
profiling the 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 15%.
13. The method of claim 12 wherein the subject administered alvocidib has an MDP determined to be at least 20%.
14. The method of claim 12 wherein the subject administered alvocidib has an MDP determined to be at least 30%.
15. The method of claim 12 wherein the profiling is performed in the absence of a permeabilizing agent.
16. A method for treating a subject having myelodysplastic syndrome (MDS) comprising:
acquiring a plurality of bone marrow cells from the subject;
profiling the 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 15%.
17. The method of claim 16 wherein the subject administered alvocidib has an MDP determined to be at least 20%.
18. The method of claim 16 wherein the subject administered alvocidib has an MDP determined to be at least 30%.
19. The method of claim 16 wherein the profiling is performed in the absence of a permeabilizing agent.