Immune effector cells pre-infected with oncolytic virus

• US 9,101,658 B2
• Filed: 05/14/2012
• Issued: 08/11/2015
• Est. Priority Date: 09/30/2005
• Status: Active Grant

• Current Assignee: Board of Trustees of the Leland Stanford Junior University (Stanford Management Co.)
• Original Assignee: Board of Trustees of the Leland Stanford Junior University (Stanford Management Co.)
• Inventors: Contag, Christopher H., Thorne, Stephen
• Primary Examiner(s): Hill, Kevin
• Application Number:
  US13/470,558
• Publication Number:
  US 20130028875A1
• Time in Patent Office: 1,184 Days
• Field of Search: 424/93.3, 424/93.71
• US Class Current: 1/1
• CPC Class Codes: A61K 2035/124 the cells being hematopoietic, bone marrow derived or blood cells
• CPC Class Codes: A61K 2039/5156 expressing foreign proteins
• CPC Class Codes: A61K 2039/5158 Antigen-pulsed cells, e.g. T-cells
• CPC Class Codes: A61K 2239/48 Blood cells, e.g. leukemia or lymphoma
• CPC Class Codes: A61K 2239/53 Liver
• CPC Class Codes: A61K 2239/55 Lung
• CPC Class Codes: A61K 2239/58 Prostate
• CPC Class Codes: A61K 2239/59 Reproductive system, e.g. uterus, ovaries, cervix or testes
• CPC Class Codes: A61K 35/13 Tumour cells, irrespective of tissue of origin tumour vaccines 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 39/461 characterised by the cell type used
• CPC Class Codes: A61K 39/464838 Viral antigens
• CPC Class Codes: A61K 48/00 Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseases; Gene therapy
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: C12N 2710/24132 Use of virus as therapeutic agent, other than vaccine, e.g. as cytolytic agent
• CPC Class Codes: C12N 5/0636 T lymphocytes
• CPC Class Codes: C12N 5/0638 Cytotoxic T lymphocytes [CTL] or lymphokine activated killer cells [LAK]
• CPC Class Codes: C12N 5/0646 Natural killers cells [NK], NKT cells

Abstract

Compositions and methods are provided for the treatment of cancer. An immune effector cell population is pre-infected with an oncolytic virus. The combined therapeutic is safe and highly effective, producing an enhanced anti-tumor effect compared to either therapy alone. The methods of the invention thus provide for a synergistic effect based on the combined biotherapeutics.

Claims

1. A method of treating cancer in a patient, the method comprising:

administering systemically to a cancer patient at least 10⁸ of human cytokine induced killer (CIK) cells infected with a oncolytic vaccinia virus in an extended eclipse phase, wherein the oncolytic vaccinia virus;

(i) is replication competent, and

(ii) comprises a genetic modification that substantially eliminates viral thymidine kinase (TK) and a genetic modification that substantially eliminates active viral growth factor (VGF);

wherein tumor cells of the cancer are reduced or eliminated.

2. The method of claim 1, wherein the patient has been previously immunized with vaccinia virus.

3. The method of claim 1, further comprising the step of repeated administration to the patient of the human cytokine induced killer (CIK) cell population infected with said oncolytic vaccinia virus.

4. The method of claim 1, wherein the cytokine induced killer (CIK) cell population is autologous to the patient.

5. The method of claim 1, wherein the cytokine induced killer (CIK) cell population is allogeneic to the patient.