Methods and compositions for treating cancer and infectious diseases

• US 11,213,583 B2
• Filed: 02/05/2015
• Issued: 01/04/2022
• Est. Priority Date: 02/05/2014
• Status: Active Grant

• Current Assignee: Cedars-Sinai Medical Center (Cedars Sinai Health System)
• Original Assignee: Cedars-Sinai Medical Center (Cedars Sinai Health System)
• Inventors: Kim, Hyung, Wang, Yanping
• Primary Examiner(s): Sang, Hong
• Application Number:
  US15/116,485
• Publication Number:
  US 20170007698A1
• Time in Patent Office: 2,525 Days
• CPC Class Codes: A61K 2039/505 comprising antibodies
• CPC Class Codes: A61K 2039/507 Comprising a combination of two or more separate antibodies
• CPC Class Codes: A61K 2039/5154 Antigen presenting cells [APCs], e.g. dendritic cells or macrophages
• CPC Class Codes: A61K 2039/545 characterised by the dose, timing or administration schedule
• CPC Class Codes: A61K 2039/55544 Bacterial toxins
• CPC Class Codes: A61K 2239/31 characterized by the route of administration
• CPC Class Codes: A61K 2239/57 Skin; melanoma
• CPC Class Codes: A61K 31/436 the heterocyclic ring system containing a six-membered ring having oxygen as a ring hetero atom, e.g. rapamycin
• CPC Class Codes: A61K 39/0011 Cancer antigens
• CPC Class Codes: A61K 39/39 characterised by the immunostimulating additives, e.g. chemical adjuvants
• CPC Class Codes: A61K 39/3955 against proteinaceous materials, e.g. enzymes, hormones, lymphokines
• CPC Class Codes: A61K 39/4611 T-cells, e.g. tumor infiltrating lymphocytes [TIL], lymphokine-activated killer cells [LAK] or regulatory T cells [Treg]
• CPC Class Codes: A61K 39/4615 Dendritic cells
• CPC Class Codes: A61K 39/4622 Antigen presenting cells
• CPC Class Codes: A61K 39/464492 Glycoprotein 100 [Gp100]
• CPC Class Codes: A61K 39/464499 Undefined tumor antigens, e.g. tumor lysate or antigens targeted by cells isolated from tumor
• CPC Class Codes: A61K 45/06 Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• CPC Class Codes: A61P 31/00 Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: C07K 16/2812 : against CD4

Abstract

The invention relates to compositions comprising a CD4 lymphocyte depleting agent; and methods of using the compositions to treat, prevent, reduce the severity of and/or slow the progression of a condition in a subject. The invention also relates to use of combinations of a CD4 lymphocyte depleting agent and at least one additional agent to treat, prevent, reduce the severity of and/or slow the progression of a condition in a subject. The additional agent may be an immune check point inhibitor, an adoptive immune therapeutic, an immune adjuvant, or an immune modulating agent, or their combinations.

Claims

1. A method of treating, reducing the severity of and/or slowing the progression of cancer in a subject in need thereof, comprising:

administering to the subject a therapeutically effective amount of an anti-CD4 antibody to deplete CD4+ regulatory T cells (Tregs) after the cancer has primed the subject'"'"'s immune system to stimulate an immune response; and

administering a therapeutically effective amount of an immune checkpoint inhibitor to the subject, thereby treating, reducing the severity of and/or slowing the progression of the cancer in the subject, wherein the immune checkpoint inhibitor is selected from the group consisting of an antibody against PD-1, an antibody against PD-L1, or a combination thereof,

wherein the administration of the anti-CD4 antibody induces interferon-gamma (IFN-γ

) response in the subject, and

wherein the cancer is melanoma, breast cancer, colon cancer, or a combination thereof.

2. The method of claim 1, wherein the subject is a human.

3. The method of claim 1, wherein the anti-CD4 antibody is a monoclonal antibody or an antigen binding fragment thereof, a polyclonal antibody or an antigen binding fragment thereof, a chimeric antibody, a humanized antibody, a human antibody or an antigen binding fragment thereof, or a single chain antibody.

4. The method of claim 1, wherein the anti-CD4 antibody is a humanized anti-CD4 antibody.

5. The method of claim 1, wherein the anti-CD4 antibody is zanolimumab.

6. The method of claim 1, wherein the anti-CD4 antibody is administered at 100-200 mg/day, 200-300 mg/day, 300-400mg/day, 400-500 mg/day, 500-600 mg/day, 600-700 mg/day, 700-800 mg/day, 800-900 mg/day, 900-1000mg/day, 1000-1100 mg/day, 1100-1200 mg/day, 1200-1300 mg/day, 1300-1400 mg/day, 1400-1500 mg/day, 1500-1600 mg/day, 1600-1700 mg/day, 1700-1800 mg/day, 1800-1900 mg/day or 1900-2000 mg/day.

7. The method of claim 1, wherein the anti-CD4 antibody and the immune checkpoint inhibitor are administered intravenously, or intraperitoneally.

8. The method of claim 1, wherein the anti-CD4 antibody and the immune checkpoint inhibitor are administered concurrently.

9. The method of claim 1, wherein the anti-CD4 antibody is administered before administering the immune checkpoint inhibitor.

10. The method of claim 1, wherein the immune checkpoint inhibitor is administered at 0.1-0.5 mg/day, 0.5-1.0 mg/day, 1.0-1.5 mg/day, 1.5-2.0 mg/day, 2.0-2.5 mg/day, 2.5-5 mg/day, 5-10 mg/day, 10-15 mg/day, 15-20 mg/day, 20-25 mg/day, 25-30 mg/day, 30-35 mg/day, 35-4 0mg/day, 40-45 mg/day, 45-50 mg/day, 50-55 mg/day, 55-60 mg/day, 60-65 mg/day, 65-70 mg/day, 70-75 mg/day, 75-80 mg/day, 80-85 mg/day, 85-90 mg/day, 90-95 mg/day or 95-100 mg/day.

11. The method of claim 1, further comprising administering an effective amount of an immune adjuvant.

12. The method of claim 11, wherein the immune adjuvant is selected from the group consisting of an aluminum salt, a virosome, an oil-based adjuvant, and a combination thereof.

13. The method of claim 1, further comprising administering to the subject a therapeutically effective amount of an immune modulating agent.

14. The method of claim 13, wherein the immune modulating agent is an mTOR inhibitor.

15. The method of claim 14, wherein the mTOR inhibitor is selected from the group consisting of (i) temsirolimus (CCI-779), (ii) evirolimus (RAD-001), and (iii) sirolimus (rapamycin).

16. The method of claim 1, further comprising administering a therapeutically effective amount of an adoptive immune therapeutic agent.

17. The method of claim 16, wherein the adoptive immune therapeutic agent is a dendritic cell vaccine.

18. The method of claim 16, wherein the adoptive immune therapeutic agent is selected from the group consisting of a dendritic cell vaccine, a peptide vaccine, an immune cytokine, a heat shock protein-based vaccine, a tumor lysate-based vaccine, and a viral vector carrying a tumor antigen.