Mammalian antigen-presenting T cells and bi-specific T cells

• US 20050129671A1
• Filed: 03/11/2004
• Published: 06/16/2005
• Est. Priority Date: 03/11/2003
• Status: Abandoned Application

• Current Assignee: City of Hope
• Original Assignee: City of Hope
• Inventors: Jensen, Michael, Cooper, Laurence
• Application Number:
  US10/797,609
• Publication Number:
  US 20050129671A1
• Time in Patent Office: Days
• US Class Current: 424/93.210
• CPC Class Codes: A61K 2039/5158 Antigen-pulsed cells, e.g. T-cells
• CPC Class Codes: A61K 2239/29 Multispecific CARs
• CPC Class Codes: A61K 2239/31 characterized by the route of administration
• CPC Class Codes: A61K 2239/38 characterised by the dose, timing or administration schedule
• CPC Class Codes: A61K 2239/48 Blood cells, e.g. leukemia or lymphoma
• CPC Class Codes: A61K 35/12 Materials from mammals; Compositions comprising non-specified tissues or cells; Compositions comprising non-embryonic stem cells; Genetically modified cells vaccines or medicinal preparations containing antigens or antibodies A61K39/00
• CPC Class Codes: A61K 35/17 Lymphocytes; B-cells; T-cells; Natural killer cells; Interferon-activated or cytokine-activated lymphocytes when activated by a specific antigen A61K39/00
• CPC Class Codes: A61K 39/0011 Cancer antigens
• CPC Class Codes: A61K 39/001112 CD19 or B4
• CPC Class Codes: A61K 39/001124 CD20
• CPC Class Codes: A61K 39/145 Orthomyxoviridae, e.g. influenza virus
• CPC Class Codes: A61K 39/245 Herpetoviridae, e.g. herpes simplex virus
• 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 39/4631 Chimeric Antigen Receptors [CAR]
• CPC Class Codes: A61K 39/4632 T-cell receptors [TCR]; antibody T-cell receptor constructs
• CPC Class Codes: A61K 39/464412 CD19 or B4
• CPC Class Codes: A61K 39/464838 Viral antigens
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: C12N 5/0636 T lymphocytes

Abstract

The present invention is directed to mammalian bi-specific T cells and methods for using these bi-specific T cells. More specifically, the invention relates to viral specific T cells that express chimeric anti-tumor receptors. These bi-specific T cell clones are a source of effector cells that persist in vivo in response to stimulation with viral antigen, leading to long-term function after their transfer to patients with cancer and autoimmune diseases.

Claims

1. A bi-specific T cell which expresses and bears on its surface a viral antigen T cell receptor and cancer antigen-specific chimeric receptor.

2. The bi-specific T cell of claim 1, wherein the chimeric T cell receptor comprises an intracellular signaling domain, a transmembrane domain and a cancer antigen-specific extracellular domain.

3. The bi-specific T cell of claim 2, wherein the cancer antigen is selected from the group consisting of CD19, CD20, neuroblastoma antigen and IL13.

4. The bi-specific T cell of claim 1, wherein the viral antigen is selected from the group consisting of influenza, EBV, CMV and adenovirus.

5. The bi-specific T cell of claim 2, wherein the viral antigen is selected from the group consisting of influenza, EBV, CMV and adenovirus.

6. The bi-specific T cell of claim 3, wherein the viral antigen is selected from the group consisting of influenza, EBV, CMV, adenovirus.

7. A method for treating cancer in a mammal comprising administering a therapeutically acceptable amount of the bi-specific T cell of any one of claims 1-6.

8. A method of abrogating an untoward B cell function in a mammal comprising administering a therapeutically acceptable amount of the bi-specific T cell of any one of claims 1-6, wherein said cancer antigen-specific chimeric T cell receptor is specific for CD19 or CD20, neuroblastoma antigen or IL-13.

9. The method of claim 8, wherein the untoward B cell function is a B-cell mediated autoimmune disease.

10. The method of claim 8, wherein the B-cell mediated autoimmune disease is lupus or rheumatoid arthritis.

11. The method of claim 7, which further comprises effecting persistence in vivo of the bi-specific T cell by administering to the mammal a stimulatory amount of a viral antigen or T-cells expressing a viral antigen, wherein the viral antigen-specific receptor of the bi-specific T cell is the same as the administered viral antigen.

12. A method for effecting persistence in vivo of the bi-specific T cell of any one of claims 1-6 comprising administering to a mammal a stimulatory amount of a viral antigen or T-cells expressing a viral antigen, wherein the viral antigen-specific receptor of the bi-specific T cell is the same as the administered viral antigen.

13. A method for effecting persistence in vivo of the bi-specific T cell of any one of claims 1-6 comprising administering ganciclovir when the bi-specific T cell co-expresses the HyTK fusion gene.

14. A method for vaccinating patients with a desired antigen by administering T cells genetically modified to express the desired antigen.

15. A method of eliminating bi-specific T cells in vivo by withdrawing administration of the viral antigen recognized by the bi-specific T cell or with-holding viral antigen recognized by the bi-specific T cell.