Granted Patent
B2
US 12,559,559 · App. 17/622,507 · Granted Feb 24, 2026
Targeting Galectin-9 as a therapeutic strategy for T-cell exhaustion in T-cell acute lymphoblastic leukemia
Inventors:
Birgit Knoechel (Brookline, MA); Jens G. Lohr (Brookline, MA); Praveen Anand (Allston, MA); Amy Guillaumet-Adkins (Allston, MA); Jon Aster (Lexington, MA)
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Abstract
The present invention relates to compositions and methods for treating early T-cell precursor acute lymphoblastic leukemia (ETP T-ALL).
Claims (19)
1 . A method of decreasing T cell exhaustion in a subject having early T-cell precursor acute lymphoblastic leukemia (ETP T-ALL), the method comprising:
identifying a subject having ETP T-ALL, and
administering to the subject an effective amount of a neutralizing anti-Galectin-9 monoclonal antibody or a Galectin-9 binding antibody fragment thereof,
thereby decreasing T cell exhaustion,
wherein the anti-Galectin-9 antibody comprises Galectin-9 monoclonal antibody 9M1-3, D9R4A, or OT1D12.
2 . The method of claim 1 , wherein T cell effector function is increased.
3 . The method of claim 1 , further comprising obtaining a test sample from the subject; and identifying malignant early T-cell precursor acute lymphoblastic leukemic cells in the test sample.
4 . The method of claim 3 , wherein the test sample is obtained from a tumor tissue, a tumor microenvironment, a plasma sample, or a blood sample.
5 . The method of claim 1 , wherein the subject has relapsed or wherein the ETP T-ALL is refractory to treatment.
6 . The method of claim 1 , further comprising administering to the subject a chemotherapeutic agent, radiation therapy, cryotherapy, hormone therapy, or immunotherapy.
7 . The method of claim 6 , wherein the chemotherapeutic agent comprises thalidomide, lenalidomide, ixazomib, bortezomib, carfilzomib, melphalan, vincristine, cyclophosphamide, doxorubicin, liposomal doxorubicin, rituximab, etoposide or bendamustine.
8 . The method of claim 6 , wherein the chemotherapeutic agent is administered with a steroid.
9 . The method of claim 8 , wherein the steroid comprises prednisone or dexamethasone.
10 . The method of claim 1 , further comprising administering to the subject a combination chemotherapy agent.
11 . The method of claim 10 , wherein the combination chemotherapy agent comprises hyper-CVAD, hyper-CVAD+nelarabine or augmented Berlin-Frankfurt-Münster (aBFM) regimen.
12 . The method of claim 1 , further comprising administering an γ-secretase inhibitor selected from the group consisting of-BMS-906024, LY411,575, MK-0752, GSI MRK-003, GSI RO4929097, GSI PF-03084014, and BMS-708163.
13 . The method of claim 1 , further comprising administering a phosphoinositide 3-kinase (PI3-K) inhibitor selected from the group consisting of BAY80-6946/Copanlisib, Duvelisib/IPI-145, and δ/γ CAL-101/idelalisib.
14 . The method of claim 1 , wherein the subject is a human.
15 . The method of claim 1 , wherein the anti-Galectin-9 monoclonal antibody or Galectin-9 binding antibody fragment thereof is partially humanized, fully humanized, or chimeric.
Assignments (1)
ASSIGNMENT OF ASSIGNOR'S INTEREST
Recorded Nov 4, 2022
From: KNOECHEL, BIRGIT; LOHR, JENS G.; ANAND, PRAVEEN; GUILLAMET-ADKINS, AMY
To: DANA-FARBER CANCER INSTITUTE, INC.
Reel/Frame 061657/0075 →
Continuity (2)
Provisional Application
62872987
· Jul 11, 2019
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