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1. (WO2019043065) METHOD AND PREPARATION FOR SORTING OUT T EFFECTOR CELLS USING ANTI-CD127 ANTIBODIES FOR APPLICATIONS IN CELL THERAPY
ملاحظة: نص مبني على عمليات التَعرف الضوئي على الحروف. الرجاء إستخدام صيغ PDF لقيمتها القانونية

Claims

A method for in vitro sorting out Teffector cells from a preparation of cells, in particular a preparation of cells obtained from a biological fluid or tissue wherein the preparation of cells comprises human cells especially human blood cells, wherein the method comprises the step of :

a. contacting the cell preparation with an antibody specifically binding to CD 127 and having a moderate affinity for CD 127 and selectively binding to Teffector cells present in the cell preparation,

b. selectively sorting out said Teffector cells and recovering the cell preparation depleted for at least Treg cells,

in particular wherein the antibody specifically binding to CD 127 does not interfere with the IL-7 signaling pathway.

The method according to claim 1, wherein the anti-CD 127 antibody comprises the following CDRs sequences:

- in the heavy chain, the CDRs of a VH3 heavy chain disclosed as sequence of SEQ ID No2, in particular CDRS of VH3-CDR1, VH3-CDR2 and VH3-CDR3 comprising or consisiting of the sequences of SEQ ID No 14, 16 and 18, respectively and,

- in the light chain, the CDRs of a VL3 or of a VL4 light chain disclosed as sequences of SEQ ID No No4 and 6, respectively, in particular CDRs VL3- CDR1, VL3/4-CDR2 and VL3/4-CDR3 having the sequences of SEQ ID No20, 22 and 24 respectively, or CDRs of VL4-CDR1, VL3/4-CDR2 and VL3/4-CDR3 comprising or consisting of the sequences of SEQ ID No26, 22 and 24 respectively.

The method according to claim 1 or 2, wherein the anti-CD 127 antibody is selected from the group of anti-CD 127 antibodies comprising VH and VL sequences as follows:

a. a heavy chain variable domain designated Effi3-VH3 comprising or consisting of sequence of SEQ ID No2 or Effi3-VH3 variant comprising or consisting of sequence SEQ ID No8 and,

for the variant designated Effi3-VH3VL3, either a light chain variable domain designated Effi3-VL3 comprising or consisting of sequence SEQ ID No4 or

Effi3-VL3 variant comprising or consisting of sequence SEQ ID No 10, or alternatively

b. a heavy chain variable domain designated Effi3-VH3 comprising or consisting of sequence of SEQ ID No2 or Effi3-VH3 variant comprising or consisting of sequence SEQ ID No8 and,

for the variant designated Effi3-VH3VL4, either a light chain variable domain designated Effi3-VL4 comprising or consisting of sequence SEQ ID No6 or Effi3-VL4 variant comprising or consisting of sequence SEQ ID No 12.

4. The method according to any one of claims 1 to 3, wherein the step of sorting out cells is performed using magnetic cell sorting and the anti-CD 127 antibody is biotinylated or otherwise marked for staining.

5. The method according to any one of claims 1 to 4, wherein cell sorting is performed until more than 90%, in particular until more than 99% of Treg cells are depleted from the preparation of cells.

6. The method according to any one of claims 1 to 5, wherein anti-CD 127 antibodies are provided with a composition that comprises polyclonal immunoglobulins, especially polyclonal human immunoglobulins, suitable for reducing nonspecific interactions of anti-CD 127 antibodies with targeted Teff cells.

7. The method according to any one of claims 1 to 6, wherein the cell preparation is a human blood cell preparation.

8. The method according to any one of claims 1 to 7, wherein the cell preparation is a preparation of hematopoietic stem cells for transplantation (HSCT) or T cells for adoptive therapy, including tumor-infiltrating cells (TILs) and/or genetically modified cancer- specific T cells such as Chimeric- Antigen Receptor T cells (CART).

9. A composition of compounds or a set of compounds comprising anti-CD 127 antibodies as defined in any one of claims 1 to 4 and polyclonal human immunoglobulins .

10. Use of the composition of claim 9 for carrying out the method according to any one of claims 1 to 8.

11. A preparation comprising or consisting of Teffector cells depleted for at least Treg cells population prepared by carrying out the method according to any one of claims 1 to 8, in particular wherein the method is carried out with the composition or the set of compounds according to claim 9.

12. A preparation according to claim 11, for the preparation of treated human cells, especially blood cells, in particular for the preparation of hematopoietic stem cells for transplantation (HSCT) or T cells for adoptive therapy, including expanded tumor- infiltrating cells (TILs) and/or genetically modified cancer-specific T cells such as Chimeric- Antigen Receptor T cells (CART).

13. A preparation according to claim 11, for the preparation of treated human cells, especially blood cells, suitable for treatment of solid or liquid tumor in a human patient or suitable for treatment of chronic infections by a pathogen selected among bacteria, parasites, protozoans, yeasts and viruses in a human patient.

14. The preparation according to any one of claims 11 to 13, wherein the level of Treg depletion is 90% or more.

15. The preparation according to any one of claims 11 to 14 for use in treating a human patient against hematologic malignancies, especially against relapsing hematologic cancer wherein a population of hematopoietic stem cells for transplantation (HSCT) depleted for at least Treg cells is administered to the patient.

16. The preparation according to any one of claims 11 to 14 for use in treating a human patient against solid tumor by adoptive T cells therapy, wherein expanded tumor- infiltrating cells (TILs) depleted for at least Treg cells population are administered to the patient or for use against solid or liquid tumor wherein genetically modified cancer- specific T cells such as Chimeric- Antigen Receptor T cells (CART) depleted for at least Treg cells population are administered to the patient.

17. The preparation according to any one of claims 11 to 14 for use in treating a chronic infection in a human patient wherein the pathogen is selected among bacteria, parasites, protozoans, yeasts and viruses.

18. A combination product comprising (i) a preparation of cells obtained after carrying out the method according to any one of claims 1 to 8, in particular wherein the method is carried out using a composition or a set of compounds according to claim 9 or a preparation of cells according to any one of claims 11 to 17 and (ii) a compound of therapeutic interest such as anti-cancer agents such as T cell activators.

19. Use of the method according to any one of claims 1 to 8, in particular wherein the method is carried out with the composition or the set of compounds according to claim 9, for the preparation of a composition comprising treated human cells depleted for Treg cells, especially blood cells, in particular a composition comprising or consisting of Teff cells and depleted for at least Treg cells population, in particular a composition of hemapoietic stem cells for transplantation (HSCT) or T cells for adoptive T cells therapy, including expanded tumor-infiltrating cells (TILs) and genetically-modified cancer specific T cells such as Chimeric- Antigen Receptor T cells (CART).

20. Use of the method according to any one of claims 1 to 8, in particular wherein the method is carried out with the composition or the set of compounds according to claim

9, for the preparation of a composition comprising treated human cells depleted for Treg cells, especially blood cells, in particular a composition comprising or consisting of Teff cells and depleted for at least Treg cells population, suitable for the treatment of solid or liquid tumor in a human patient or suitable for the treatment of chronic infections by a pathogen selected among bacteria, parasites, protozoans, yeasts and viruses in a human patient.