CELL POPULATION FOR USE IN TRETING CANCER

Abstract

The invention pertains to a cell population for use in treating cancer in a patient, comprising CD1c (BDCA-1).sup.+/CD19.sup.− dendritic cells, wherein CD1c(BDCA-1).sup.+/CD19.sup.− dendritic cells are depleted for CD1c (BDCA-1).sup.+/CD197CD14.sup.+ cells.

Claims

1.-15. (canceled)

16. A cell population for use in treating cancer in a patient, comprising CD1c+/CD19− dendritic cells, wherein less than or equal to 25% of the CD1c+/CD19− dendritic cells are CD1c+/CD19−/CD14+ cells.

17. The cell population of claim 16, wherein at least 50% of the cells are loaded with a tumor antigen or a tumor peptide.

18. The cell population of claim 16, wherein the cell population further comprises cells that are also CD304+ (BDCA-4+).

19. The cell population of claim 18, wherein at least 50% of the cells are loaded with a tumor antigen or a tumor peptide.

20. The cell population of claim 16, wherein the cells are purified from blood of the patient to be treated for cancer.

21. The cell population of claim 16, wherein the cancer is a solid cancer or a blood cancer.

22. The cell population of claim 21, wherein the cancer is chronic myeloid leukemia.

23. The cell population of claim 21, wherein the cancer is melanoma or prostate cancer.

24. Use of a kit for producing a cell population for treating cancer in a patient, the kit comprising: an antibody capable of binding to CD1c (BDCA-1), an antibody capable of binding to a marker expressed on monocytes, an antibody capable of binding to a marker expressed on B-lymphocytes, in particular CD19 or CD20, and, optionally an antibody capable of binding to plasmacytoid dendritic cells.

25. The use of claim 24, further comprising a tumor antigen or a tumor peptide.

26. The use of claim 24, wherein the B cell marker is selected from the group consisting of CD19 and CD20.

27. The use of claim 26, further comprising a tumor antigen or a tumor peptide.

28. The use of claim 24, wherein the monocyte marker is selected from the group consisting of CD14, CD11b, and CCR5.

29. The use of claim 28, wherein the B cell marker is selected from the group consisting of CD19 and CD20.

30. The use of claim 29, further comprising a tumor antigen or a tumor peptide.

31. A method for treating cancer, comprising administering a cell population of claim 16 to a patient diagnosed with cancer.

Description

FIGURES

[0104] The figures show:

[0105] FIG. 1: BDCA1+CD14+DCs are associated with cancer.

[0106] FIG. 1A. The percentage of BDCA1+CD14+ cells is increased in cancer patients.

[0107] FIG. 1B. Higher percentages of BDCA1+CD14+ in ovarian cancer asites.

[0108] FIG. 1C. Phenotyping different cell subsets.

[0109] FIG. 2A. BDCA1+CD14+ population is a unique subset as shown by transcriptome analysis.

[0110] FIG. 2B. Expression of transcription factors that were described to be involved in myeloid development in mice.

[0111] FIG. 2C. Expression of growth factor receptors that were described to be involved in myeloid development in mice.

[0112] FIG. 3. BDCA1+ CD14+ population is a unique subset as shown by multiplex analysis.

[0113] FIG. 4: BDCA1+CD14+ cells possess DC characteristics.

[0114] FIG. 4A. BDCA1+CD14+ cells are very efficient in antigen uptake.

[0115] FIG. 4B. BDCA1+CD14+ cells upregulate the costimulatory molecule CD80 upon stimulation with TLR ligands.

[0116] FIG. 4C. BDCA1+CD14+ cells possess a unique inflammatory cytokine profile.

[0117] FIG. 5A. MLR

[0118] FIG. 5B. Nave T cell stimulatory capacity.

[0119] FIG. 6: The reduced activity of BDCA1+CD14+ cells is caused by PD-L1 and MERTK expression.

[0120] FIG. 6A: BDCA1+CD14+ DCs upregulate PD-L1 in response to TLR stimulation.

[0121] FIG. 6B: PD-L1 blocking enhances the T cell stimulatory capacity of BDCA1+CD14+.

[0122] FIG. 7: BDCA1+CD14+ cells are associated with lower response towards cancer immunotherapy in melanoma patients.

[0123] FIG. 7A: Higher percentages of BDCA1+CD14+ cells in myeloid DC immunotherapy correlate with lower responses in patients.

[0124] FIG. 7B: BDCA1+CD14+ DCs suppress the proliferation of KLH-specific CD4+T cells.

[0125] FIG. 7B: BDCA1+CD14+ DCs suppressor capacity is inhibited by Oxaliplatin.

[0126] FIG. 7C: BDCA1+CD14+ DCs do not suppress polyclonal T cell proliferation.

[0127] FIG. 8: A possible sorting strategy.

[0128] FIG. 9: A composition of the invention is the “BDCA-1 enriched” cell population. According to the invention, the fraction of BDCA1+CD14+ need to be diminished to less than 25% of the total cells in order to obtain a cell population for administration to a patient suffering from cancer.