METHODS OF OBTAINING MONONUCLEAR BLOOD CELLS AND USES THEREOF
Methods of obtaining mononuclear blood cells are provided. Also provided are methods of using the obtained cells for treating diseases such as cancer, infectious disease, autoimmune disease, allergy, and graft rejection.
1 . A method of obtaining dendritic cells (DCs) from a subject, the method comprising:
(a) administering to the subject an effective amount of a peptide having an amino acid sequence as set forth in SEQ ID NO:1 or an analog or derivative thereof; and
(b) collecting peripheral blood of said subject 4-8 hours following said administering;
thereby obtaining the DCs from the subject.
2 . A method of obtaining at least one type of mononuclear blood cells (MNBCs) selected from the group consisting of T cells, B cells, NK cells and NKT cells from a subject, the method comprising:
(a) administering to the subject an effective amount of a peptide having an amino acid sequence as set forth in SEQ ID NO:1 or an analog or derivative thereof;
(b) collecting peripheral blood of said subject 4-48 hours following said administering; and optionally
(c) repeating step (b) at least once no later than 48 hours following said administering;
thereby obtaining the at least one type of MNBCs from the subject.
3 . The method of claim 2 , wherein said MNBCs comprise T cells.
4 . The method of claim 2 , further comprising purifying said MNBCs from said peripheral blood following said collecting.
5 . A method of obtaining cells effective for the treatment of cancer, the method comprising:
(a) administering to a subject an effective amount of a peptide having an amino acid sequence as set forth in SEQ ID NO:1 or an analog or derivative thereof;
(b) collecting peripheral blood of said subject; and
(c) enriching from said peripheral blood at least one type of mononuclear blood cells (MNBCs) capable of eliciting an immune response against a cancerous cell,
thereby obtaining the cells effective for the treatment of cancer.
6 . The method of claim 5 , wherein said enriching comprises purifying at least one type of MNBCs selected from the group consisting of dendritic cells (DCs), T cells, B cells, NK cells and NKT cells from said peripheral blood following said collecting.
7 . The method of claim 5 , wherein said cells are selected from the group consisting of dendritic cells (DCs), T cells, B cells, NK cells and NKT cells.
8 . The method of claim 5 , wherein said cells comprise dendritic cells (DCs).
9 . The method of claim 8 , wherein said DCs comprise immature DCs.
10 . The method of claim 5 , wherein when said cells comprise immature DCs the method comprises inducing maturation of said immature DCs or T cells.
11 . (canceled)
12 . The method of claim 5 , wherein said enriching is effected by a method selected from the group consisting of:
(i) selecting anti-cancer reactive cells;
(ii) activating anti-cancer reactive cells;
(iii) expanding anti-cancer reactive cells;
(iv) promoting presentation of a cancer antigen; and
(v) promoting presentation of an anti-cancer receptor.
13 . The method of claim 12 , wherein said enriching comprises contacting said peripheral blood or a purified population of cells thereof with a cancer antigen selected from the group consisting of a cancer antigenic peptide or polypeptide, a cancer cell lysate, a cancerous cell and a DC presenting a cancer antigen.
14 . The method of claim 12 , wherein said activating or expanding comprises contacting said peripheral blood or a purified population of cells thereof with a cytokine capable of inducing activation and/or proliferation of a T cell.
15 . The method of claim 12 , wherein said activating comprises contacting said peripheral blood or a purified population of cells thereof with a co-stimulatory molecule.
16 . The method of claim 15 , wherein said co-stimulatory molecule is selected form the group consisting of an immune-check point regulator, LPS and TLR ligands.
17 . The method of claim 16 , wherein said immune-check point regulator is selected from the group consisting of anti-CTLA4, anti-PD-1 and CD40 agonist.
18 . The method of claim 12 , wherein when said cells comprise T cells, said promoting presentation of an anti-cancer receptor comprises transducing with a T cell receptor (TCR) or a chimeric antigen receptor (CAR).
19 . The method of claim 12 , wherein when said cells comprise DCs said promoting presentation of a cancer antigen comprises transfecting with an mRNA coding for a cancer antigen.
20 . A method of treating cancer in a subject in need thereof, the method comprising:
(a) obtaining cells effective for the treatment of cancer according to the method of claim 5 ; and
(b) transplanting said cells to a subject, thereby treating the cancer in the subject.
21 . The method of claim 20 , wherein when said cells comprise DCs, said transplanting is in combination with an adjuvant.
22 . The method of claim 20 , wherein said transplanting is in combination with an anti-cancer immune modulator agent.
23 . The method of claim 22 , wherein said transplanting is effected prior to the treatment with said agent.
24 . The method of claim 22 , wherein said transplanting is effected concomitant with the treatment with said agent.
25 . The method of claim 22 , wherein said transplanting is effected following the treatment with said agent.
26 . The method of claim 22 , wherein said agent is selected from the group consisting of a cancer antigen, a cancer vaccine, an anti-cancer antibody, a cytokine capable of inducing activation and/or proliferation of a T cell and an immune-check point regulator.
27 . The method of claim 14 , wherein said cytokine is selected from the group consisting of IL-2, IFNα and IL-12.
28 . (canceled)
29 . A method of obtaining cells effective for the treatment of an infectious disease, the method comprising:
(a) administering to a subject an effective amount of a peptide having an amino acid sequence as set forth in SEQ ID NO:1 or an analog or derivative thereof;
(b) collecting peripheral blood of said subject; and
(c) obtaining from said peripheral blood at least one type of mononuclear blood cells (MNBCs) capable of eliciting an immune response against a pathogen,
thereby obtaining the cells effective for the treatment of the infectious disease.
30 . The method of claim 29 , wherein said cells are selected from the group consisting of memory T cells, pathogen-specific T cells and DCs presenting a pathogenic antigen.
31 . A method of treating an infectious disease in a subject in need thereof, the method comprising:
(a) obtaining cells effective for the treatment of an infectious disease in a subject according to the method of claim 29 ; and
(b) transplanting said cells to a subject,
thereby treating the infectious disease in the subject.
32 . A method of obtaining cells effective for treatment of an autoimmune disease, allergy or graft rejection disease, the method comprising:
(a) administering to a subject an effective amount of a peptide having an amino acid sequence as set forth in SEQ ID NO:1 or an analog or derivative thereof;
(b) collecting peripheral blood from said subject;
(c) obtaining from said peripheral blood at least one type of mononuclear blood cells (MNBCs) capable of inducing tolerance to an autoimmune cell an allergen or a graft;
thereby obtaining the cells effective for treatment of the autoimmune disease, allergy or graft rejection disease.
33 . The method of claim 32 , wherein said cells are selected from the group consisting of regulatory DCs, immature DCs and regulatory T cells.
34 . A method of treating an autoimmune disease, allergy or graft rejection disease in a subject in need thereof, the method comprising:
(a) obtaining cells effective for treatment of an autoimmune disease, allergy or graft rejection disease in a subject according to the method of claim 32 ; and
(b) transplanting said cells to a subject,
thereby treating the autoimmune disease, allergy or graft rejection disease in the subject.
35 . A method of transplanting a graft in a subject in need, the method comprising:
(a) transplanting the graft in the subject;
(b) obtaining cells according to the method of claim 1 ; and
(c) transplanting said cells to said subject,
thereby transplanting the graft in the subject.
36 - 50 . (canceled)
51 . The method of claim 1 , wherein said peptide is as set forth in SEQ ID NO: 1.
52 . The method of claim 1 , wherein said cells do not comprise CD34+ hematopoietic stem/progenitor cells.