ELIMINATION OF CD19-POSITIVE LYMPHOID MALIGNANCIES BY CD19-CAR EXPRESSING NK CELLS
Provided herein are compositions of NK-92® cells that express a CD19 CAR, CD16 and IL2, and the method of using these cells to and treat cancer in a patient.
1 . A method of treating cancer in a subject, the method comprising administering to the subject a therapeutically effective amount of a composition comprising genetically engineered natural killer (NK) cells expressing an anti-cluster of differentiation 19 (CD19) chimeric antigen receptor, wherein the anti-CD19 CAR comprises an antigen binding domain comprising a CD19-specific single chain variable fragment (scfv), wherein the C-terminus of the scfv is fused via a peptide linker to the N-terminus of a hinge domain, wherein an intracellular signaling domain comprises the hinge domain at its N-terminus, a transmembrane domain, and an FcεRIγ cytoplasmic signaling domain at its C-terminus, and wherein the intracellular signaling domain has the amino acid sequence of amino acids 274-407 of SEQ ID NO: 12.
2 . The method of claim 1 , wherein 1×10 8 to 1×10 11 NK cells per m 2 of body surface area of the subject are administered to the subject.
3 . The method of claim 1 , wherein 1×10 8 to 1×10 10 NK cells are administered to the subject.
4 . The method of claim 1 , wherein 1×10 9 NK cells are administered to the subject.
5 . The method of claim 1 , wherein the cancer is a leukemia or a lymphoma.
6 . The method of claim 1 , wherein the cancer is one or more of B-cell malignancy, B-cell malignancy post-hematopoietic stem cell transplantation (HSCT), acute lymphoblastic leukemia (ALL), B-lineage lymphoid malignancy post-Umbilical Cord Blood Transplantation (UCBT), chronic lymphocytic leukemia (CLL), B-Non-Hodgkin's Lymphoma (B-NHL), ALL post-HSCT; lymphoma, refractory follicular lymphoma, or Lymphoblastic leukemia.
7 . The method of claim 6 , wherein the B-cell malignancy is a B-NHL.
8 . The method of claim 6 , wherein the B-cell malignancy is a ALL.
9 . The method of claim 6 , wherein the B-cell malignancy is a CLL.
10 . The method of claim 1 , wherein the NK cells are administered intravenously and/or intratumorally.
11 . The method of claim 1 , wherein the NK cells are administered to the subject multiple times.
12 . The method of claim 11 , wherein the NK cells are administered to the subject once every 7 days.
13 . The method of claim 1 , wherein the NK cell is an NK-92 cell.
14 . The method of claim 13 , wherein the NK-92 is genetically engineered to express interleukin-2 (IL-2) or interleukin-15 (IL-15).
15 . The method of claim 1 , further comprising administration of an antibody.
16 . The method of claim 15 , wherein the antibody is an anti-CD20 antibody.
17 . The method of claim 16 , wherein the anti-CD20 antibody is Rituximab.
18 . The method of claim 15 , wherein the NK cells and the antibody are administered on the same day.