Treatment of cancer with nk cells and a cd20 targeted antibody
AssigneeArtiva Biotherapeutics, Inc.
InventorsSungyoo CHO, Yu Kyeong HWANG, Eunji CHOI, Miyoung JUNG, Hoyong LIM, Eunsol LEE, Hansol KIM, Peter FLYNN, Jason B. LITTEN, Thomas James FARRELL, John Kin Chuan LIM, Mili MANDAL
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Abstract
Provided herein are, among other things, methods for treating a patient suffering from a CD20+ cancer.
Claims67
A method for treating a patient suffering from a CD20+ cancer, the method comprising administering a population of natural killer cells (NK cells) and an antibody targeted to human CD20, wherein the NK cells are allogenic to the patient, are KIR-B haplotype and homozygous for a CD16 158V polymorphism.
The method any one of the foregoing claims, wherein the patient has relapsed after treatment with an anti-CD20 antibody.
The method of any one of the foregoing claims, wherein the patient has experienced disease progression after treatment with autologous stem cell transplant or chimeric antigen receptor T-cell therapy (CAR-T).
The method of any one of the foregoing claims, wherein the patient is administered 1×108 to 1×1010 NK cells.
The method of any one of the foregoing claims, wherein the patient is administered 1×109 to 8×109 NK cells.
The method of any one of the foregoing claims, wherein the patient is administered 4×108, 1×109, 4×109, or 8×109 NK cells.
The method of any of the forgoing claims, wherein the antibody is selected from the group consisting of obinutuzumab (or a biosimilar thereof), ofatumumab (or a biosimilar thereof), or combinations thereof.
The method of any of the forgoing claims, wherein the patient is subjected to lymphodepleting chemotherapy prior to treatment.
The method of any of the forgoing claims further comprising administering IL-2.
The method of any of the forgoing claims wherein the administration of the NK cells and the antibody targeted to human CD20 occurs weekly.
The method of any of the forgoing claims wherein the NK cells and the antibody targeted to human CD20 are administered weekly for 4 to 8 weeks.
The method of any of the forgoing claims wherein the administration of the NK cells occurs weekly and the administration of the antibody targeted to human CD20 occurs every other week.
The method of any of the forgoing claims, wherein the NK cells are not genetically modified.
The method of any of the forgoing claims, wherein at least 70% of the NK cells are CD56+ and CD16+.
The method of any of the forgoing claims, wherein at least 85% of the NK cells are CD56+ and CD3−.
The method of any of the forgoing claims, wherein 1% or less of the NK cells are CD3+, 1% or less of the NK cells are CD19+ and 1% or less of the NK cells are CD14+.
The method of any of the forgoing claims wherein the each administration of NK cells is administration of 1×109 to 5×109 NK cells.
The method of any of the forgoing claims wherein the patient receives a dose of the CD20 targeted antibody before the first dose of NK cells.
The method of any of the forgoing claims, wherein the expanded natural killer cells are expanded umbilical cord blood natural killer cells.
The method of any of the forgoing claims, wherein the population of expanded natural killer cells comprises at least 60%, e.g., at least 70%, at least 80%, at least 90% at least 95%, at least 99%, or 100% CD16+ cells.
The method of any of the forgoing claims, wherein the population of expanded natural killer cells comprises at least 60%, e.g., at least 70%, at least 80%, at least 90% at least 95%, at least 99%, or 100% NKG2D+ cells.
The method of any of the forgoing claims, wherein the population of expanded natural killer cells comprises at least 60%, e.g., at least 70%, at least 80%, at least 90% at least 95%, at least 99%, or 100% NKp46+ cells.
The method of any of the forgoing claims, wherein the population of expanded natural killer cells comprises at least 60%, e.g., at least 70%, at least 80%, at least 90% at least 95%, at least 99%, or 100% NKp30+ cells.
The method of any of the forgoing claims, wherein the population of expanded natural killer cells comprises at least 60%, e.g., at least 70%, at least 80%, at least 90% at least 95%, at least 99%, or 100% DNAM-1+ cells.
The method of any of the forgoing claims, wherein the population of expanded natural killer cells comprises at least 60%, e.g., at least 70%, at least 80%, at least 90% at least 95%, at least 99%, or 100% NKp44+ cells.
The method of any of the forgoing claims, wherein the population of expanded natural killer cells comprises less than 20%, e.g., 10% or less, 5% or less, 1% or less, 0.5% or less, or 0% CD3+ cells.
The method of any of the forgoing claims, wherein the population of expanded natural killer cells comprises less than 20% or less, e.g., 10% or less, 5% or less, 1% or less, 0.5% or less, or 0% CD14+ cells.
The method of any of the forgoing claims, wherein the population of expanded natural killer cells comprises less than 20% or less, e.g., 10% or less, 5% or less, 1% or less, 0.5% or less, or 0% CD19+ cells.
The method of any of the forgoing claims, wherein the population of expanded natural killer cells comprises less than 20% or less, e.g., 10% or less, 5% or less, 1% or less, 0.5% or less, or 0% CD38+ cells.
The method of any of the forgoing claims, wherein the natural killer cells do not comprise a CD16 transgene.
The method of any of the forgoing claims, wherein the natural killer cells do not express an exogenous CD16 protein.
The method of any of the forgoing claims, wherein the expanded natural killer cells are not genetically engineered.
The method of any of the forgoing claims, wherein the expanded natural killer cells are derived from the same umbilical cord blood donor.
The method of any of the forgoing claims, wherein the population of NK cells comprises at least 100 million expanded natural killer cells, e.g., 200 million, 250 million, 300 million, 400 million, 500 million, 600 million, 700 million, 750 million, 800 million, 900 million, 1 billion, 2 billion, 3 billion, 4 billion, 5 billion, 6 billion, 7 billion, 8 billion, 9 billion, 10 billion, 15 billion, 20 billion, 25 billion, 50 billion, 75 billion, 80 billion, 9-billion, 100 billion, 200 billion, 250 billion, 300 billion, 400 billion, 500 billion, 600 billion, 700 billion, 800 billion, 900 billion, 1 trillion, 2 trillion, 3 trillion, 4 trillion, 5 trillion, 6 trillion, 7 trillion, 8 trillion, 9 trillion, or 10 trillion expanded natural killer cells.
The method of any of the forgoing claims, wherein the population of NK cells is produced by a method comprising:
- (a) obtaining seed cells comprising natural killer cells from umbilical cord blood;
- (b) depleting the seed cells of CD3+ cells;
- (c) expanding the natural killer cells by culturing the depleted seed cells with a first plurality of Hut78 cells engineered to express a membrane bound IL-21, a mutated TNFα, and a 4-1BBL gene to produce expanded natural killer cells,
- thereby producing the population of expanded natural killer cells.
The method of any of the forgoing claims, wherein the population of NK cells is produced by a method comprising:
- (a) obtaining seed cells comprising natural killer cells from umbilical cord blood;
- (b) depleting the seed cells of CD3+ cells;
- (c) expanding the natural killer cells by culturing the depleted seed cells with a first plurality of Hut78 cells engineered to express a membrane bound IL-21, a mutated TNFα, and a 4-1BBL gene to produce a master cell bank population of expanded natural killer cells;
- and
- (d) expanding the master cell bank population of expanded natural killer cells by culturing with a second plurality of Hut78 cells engineered to express a membrane bound IL-21, a mutated TNFα, and a 4-1BBL gene to produce expanded natural killer cells;
- thereby producing the population of expanded natural killer cells.
Dependencies are inferred from the claim text.