Use of ADCC-optimized antibodies for treating low-responder patients
The invention concerns the use of human or humanized chimeric monoclonal antibodies which are produced in selected cell lines, said antibodies bringing about a high ADCC activity as well as a high secretion of cytokines and interleukins, for treating underpopulations of so-called weak-response patients exhibiting CD16 FCGR3A-158F homozygote or FCGR3A-158V/F heterozygote polymorphism.
1. A method for treating haemolytic disease of the newborn, Sezary Syndrome, chronic myeloid leukaemias, chronic lymphoid leukaemias (CLL-B), cancer, breast cancer, conditions related to the environment, infectious diseases, chronic fatigue syndrome (CFS), parasitic infections, or viral infections, comprising:
administering a composition of antibodies specific to the condition to be treated, wherein the condition to be treated has a number of antigenic sites below 250,000 per target cell,
to a patient homozygous for phenylalanine in position 158 of CD16 (FCGR3A-158F homozygotes) or heterozygous for valine/phenylalanine in position 158 of CD16 (FCGR3A-158V/F),
wherein said antibodies are biantennary type,
wherein said antibodies have an ADCC level via CD16 (FcgammaRIIla) above 60% compared with the same antibody produced in a CHO line.
2. The method according to claim 1 , wherein said patient is homozygous for phenylalanine in position 158 of CD16 (FCGR3A-158F homozygotes).
3. The method according to claim 1 , wherein the condition to be treated has a number of antigenic sites below 100,000 per target cell.
4. The method according to claim 3 , wherein the condition to be treated has a number of antigenic sites below 50,000 per target cell.
5. The method according to claim 3 , wherein the condition to be treated has a number of antigenic sites below 10,000 per target cell.
6. The method according to claim 1 , wherein the dose of said antibody administered to the patient is between 2 and 100 times lower than a dose of an antibody of the same specificity but of different glycosylation or produced in a CHO line.
7. The method according to claim 6 , wherein the dose of said antibody administered to the patient is between 5 and 25 times lower than a dose of an antibody of the same specificity but of different glycosylation or produced in a CHO line.
8. The method according to claim 1 , wherein said method is for treating a cancer of positive HLA class-II cells, B-cell lymphomas, acute B-cell leukaemias, Burkitt's syndrome, Hodgkin's lymphoma, myeloid leukaemias, chronic B-cell lymphoid leukaemias (CLL-B), non-Hodgkin's T-cell leukaemias and lymphomas and chronic myeloid leukaemias.
9. The method according to claim 1 , wherein the antibody is selected from the group consisting of anti-HLA-DR, anti-CD20, anti Ep-CAM, anti HER2, anti CD52, anti HER1, anti GD3, anti CA125, anti GD, anti GD2, anti CD-23 and anti Protein C, anti-KIR3DL2, anti-EGFR, anti-CD25, anti-CD38, anti-CD30, anti-CD33, anti- CD44, anti-Rhesus, and anti-viral antibodies.
10. The method according to claim 9 , wherein the antibody is anti-HLA-DR.
11. The method according to claim 9 , wherein the antibody is anti-CD20.
12. The method according to claim 1 , wherein said antibodies have an ADCC level via CD16 (FcgammaRIIIa) above 70% compared with the same antibody produced in a CHO line.
13. The method according to claim 1 , wherein said antibodies have an ADCC level via CD16 (FcgammaRIIIa) above 80% compared with the same antibody produced in a CHO line.
14. The method according to claim 1 , wherein said antibodies have an ADCC level via CD16 (FcgammaRIIIa) above 90% compared with the same antibody produced in a CHO line.