ANTI-EGFR/HIGH AFFINITY NK-CELLS COMPOSITIONS AND METHODS FOR CHORDOMA TREATMENT
Chordoma is treated in a patient by co-administration of an anti-EGFR antibody and high affinity NK cells (haNK). Most preferably, the antibody is non-covalently bound to a high affinity variant of a CD16 receptor or administered before transfusion of the haNK cells to so target the chordoma cells for cytotoxic cell killing by the haNK cells.
1 . A method of treating chordoma, comprising:
co-administering an anti-EGFR antibody and a high affinity NK (haNK) cell to a patient in need thereof at a dosage effective to treat the chordoma.
2 . The method of claim 1 wherein the anti-EGFR antibody is a monoclonal antibody with binding specificity against human EGFR.
3 - 14 . (canceled)
15 . The method of claim 1 wherein the further cancer treatment comprises an immune therapy.
16 . The method of claim 15 wherein the immune therapy comprises administration of a recombinant yeast or recombinant virus expressing a patient- and tumor-specific neoepitope.
17 . The method of claim 15 wherein the immune therapy comprises administration of a recombinant yeast or recombinant virus expressing brachyury.
18 . The method of claim 1 wherein the further cancer treatment comprises a chemotherapy.
19 . The method of claim 1 wherein the chemotherapy comprises administration of at least one of aldoxorubicin, cyclophosphamide, irinotecan, gemcitabine, capecitabine, 5-FU, FOLFIRI, FOLFOX, and oxiplatin.
20 . The method of claim 1 wherein the further cancer treatment comprises a radiotherapy.
21 . The method of claim 1 wherein the anti-EGFR antibody is a monoclonal antibody with binding specificity against human EGFR.
22 . The method of claim 1 wherein the anti-EGFR antibody is an IgG1.
23 . The method of claim 1 wherein the anti-EGFR antibody is a humanized non-human anti-EGFR antibody.
24 . The method of claim 1 wherein the anti-EGFR antibody is cetuximab.
25 . The method of claim 1 wherein the anti-EGFR antibody is administered at a dosage of between 100 mg/m2 and 1,000 mg/m2.
26 . The method of claim 1 wherein the anti-EGFR antibody is co-administered at the same time as the haNK cell.
27 . The method of claim 1 wherein the anti-EGFR antibody is bound to a high-affinity CD16 that is expressed on a surface of the haNK cell.
28 . The method of claim 1 wherein the haNK cell is administered at a dosage of between 5×10 5 cells/kg and 5×10 8 cells/kg.
29 . The method of claim 1 wherein the haNK cell is a NK92 derivative that further express recombinant IL2.
30 . (canceled)
31 . The method of claim 1 wherein the haNK cell is genetically engineered to have a reduced expression of at least one inhibitory receptor.
32 . The method of claim 1 wherein the haNK cell is irradiated before administration at a radiation dose of at least 500 cGy.
33 . The method of claim 1 further comprising a step of administering a further cancer treatment to the patient.
34 . The method of claim 33 wherein the further cancer treatment comprises an immune therapy.
35 . The method of claim 34 wherein the immune therapy comprises administration of a recombinant yeast or recombinant virus expressing a patient- and tumor-specific neoepitope.
36 . The method of claim 34 wherein the immune therapy comprises administration of a recombinant yeast or recombinant virus expressing brachyury.
37 . The method of claim 33 wherein the further cancer treatment comprises a chemotherapy or radiotherapy.
38 . The method of claim 37 wherein the chemotherapy comprises administration of at least one of irinotecan, gemcitabine, capecitabine, 5-FU, FOLFIRI, FOLFOX, and oxiplatin.
39 . The method of claim 33 wherein the further cancer treatment comprises a radiotherapy.
40 . A pharmaceutical composition comprising an anti-EGFR antibody and a genetically engineered NK cell, wherein a high affinity variant of CD16 is expressed on a surface of the genetically engineered NK cell, and wherein the anti-EGFR antibody is optionally bound to the high affinity variant of CD16 of the genetically engineered NK cell.
41 . The pharmaceutical composition of claim 40 wherein the antibody is a monoclonal antibody.
42 - 43 . (canceled)
44 . The pharmaceutical composition of claim 40 wherein the antibody is cetuximab.
45 - 49 . (canceled)
50 . The pharmaceutical composition of claim 40 wherein the antibody is a monoclonal antibody.
51 - 54 . (canceled)
55 . The pharmaceutical composition of claim 40 wherein the genetically engineered NK cell further expresses recombinant IL2.
56 . The pharmaceutical composition of claim 40 wherein the genetically engineered NK cell is genetically engineered to have a reduced expression of at least one inhibitory receptor.
57 . (canceled)
58 . The pharmaceutical composition of claim 40 wherein the composition is formulated for transfusion and comprises between 1×10 6 cells and 5×10 9 cells.
59 - 75 . (canceled)