# US 6,524,587 B1 · Hyperthermia and immunotherapy for leukemias lymphomas, and solid tumors

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- Number: US 6,524,587 B1
- Document ID: US6524587B1
- Status: Granted
- Kind: B1
- Application number: 09/499,050
- Filed: 2000-02-04
- Granted: 2003-02-25
- Earliest claimed: 1998-05-05
- Inventors: Bruce W. Lyday
- Web page: https://patentgrep.com/patent/US6524587B1

## CPC

- A61K 35/768: Oncolytic viruses not provided for in groups A61K35/761 - A61K35/766
- A61K 39/39: characterised by the immunostimulating additives, e.g. chemical adjuvants
- A61K 40/19: Dendritic cells
- A61K 40/24: Antigen-presenting cells [APC]
- A61K 40/42: Cancer antigens
- A61P 35/00: Antineoplastic agents
- C12N 7/00: Viruses; Bacteriophages; Compositions thereof; Preparation or purification thereof (preparing medicinal viral antigen or antibody compositions, e.g. virus vaccines, A61K39/00)
- C12N 2770/24132: Use of virus as therapeutic agent, other than vaccine, e.g. as cytolytic agent
- C12N 2770/24151: Methods of production or purification of viral material
- Y02A 50/30: Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change
- A61K: PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES (devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms A61J3/00; chemical aspects of, or use of materials for deodorisation of air, for disinfection or sterilisation, or for bandages, dressings, absorbent pads or surgical articles A61L; soap compositions C11D)
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- C12N: MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA (microbiological testing media C12Q1/00)
- Y02A: TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE

## Abstract

An improved method of inducing whole-body hyperthermia and enhanced anti-tumor immune response through inoculation of a fever virus with nil mortality and subsequent injection of irradiated tumor cells derived from the patient. This therapy will safely reduce the tumor burden by 90-99.9% by physical means (fever), before raising interferon levels to over 250 times baseline. The Activated Lymphokine Killer cells produced by these high interferon levels are capable of killing any cell expressing viral or tumor antigens, even those which had previously escaped immune surveillance. As a final step in the process, a specific class of Cytotoxic T Lymphocytes programmed to destroy the patient's own cancer cells will be produced by repeated inoculation of irradiated cancer cells harvested from the patient. Through a combination of three methods of therapy never previously integrated into a single regimen, it is logical to state that this therapy has a high probability of completely eradicating cancer cells from the patient. In addition, this therapy provides for life-long immunity to the reoccurrence of the disease.

## Claims

### Claim 1

A method of reducing tumor burden in a cancer patient with a human solid tumor, comprising the steps of:
injecting said patient with substantially pure Dengue Virus; and
maintaining body temperature of said patient in excess of 103.5 degrees F. for a sufficient period of time to reduce tumor burden, wherein said Dengue virus injection maintains said body temperature in excess of 103.5 degrees.

### Claim 2 (depends on 1)

The method of claim 1 wherein said virus is selected from the group consisting of Dengue Type 1, Type 2, Type 3, and Type 4 Serotypes of the Family Togaviridae.

### Claim 3 (depends on 1)

The method of claim 1 wherein said substantially pure Dengue Virus has been tested to confirm the elimination of neurovirulence by passing said virus through subhuman primates.

### Claim 4 (depends on 1)

The method of claim 1 wherein the purification of said substantially pure Dengue virus begins with passage of said virus through cells with an active transmembrane gradient.

### Claim 5 (depends on 4)

The method of claim 4 wherein said cells are infected with virus at less than 5 log10 plaque-forming units/ml.

### Claim 6 (depends on 1)

The method of claim 1 further comprising injecting said patient with allogenic Dendritic cells pulsed with tumor peptides; and repeating the injection of said Dendritic Cells in said patient until cancer cells in said patient are reduced.

### Claim 7 (depends on 4)

The method of claim 4 wherein said cells with an active transmembrane gradient are Green Monkey Kidney cells.

### Claim 8

A method of reducing tumor burden in a cancer patient with leukemia or lymphoma comprising the steps of;
injecting said patient with substantially pure Dengue Virus; and
maintaining body temperature of said patient in excess of 103.5 degrees F. for a sufficient period of time to reduce tumor burden, wherein said Dengue virus injection maintains said body temperature in excess of 103.5 degrees F.

### Claim 9 (depends on 8)

The method of claim 8 wherein the purification of said substantially pure Dengue virus begins with passage of said virus through cells with an active transmembrane gradient.

### Claim 10 (depends on 8)

The method of claim 8 wherein said cells are infected with virus at less than 5 log10 plaque-forming units/ml.

### Claim 11 (depends on 8)

The method of claim 8 further comprising injecting said patient with allogenic Dendritic cells pulsed with tumor peptides; and repeating the injection of said Dendritic Cells in said patient until cancer cells in said patient are reduced.

### Claim 12 (depends on 6)

The method of claim 6 wherein said cancer cells are melanoma cells and said tumor peptide is selected from the group consisting of: Melan-A/MART-1, gp100, pme17, and the MAGE group antigens.

### Claim 13 (depends on 6)

The method of claim 6 wherein said cancer cells are adenocarcinoma cells of the breast and said tumor peptide is CarcinoEmbryonic Antigen (CEA) or HER-2/neu.

### Claim 14 (depends on 6)

The method of claim 6 wherein said cancer cells are Cervical cancer cells and said tumor peptide is selected from the group consisting of any proteins from Human Papiloma Virus type 17 or 19.

### Claim 15 (depends on 6)

The method of claim 6 wherein said cancer cells are Colon cancer cells and said tumor peptide is CarcinoEmbryonic Antigen (CEA) or HER-2/neu.

### Claim 16 (depends on 6)

The method of claim 6 wherein said cancer cells are gastric cancer cells and said tumor peptide is HER-2/neu.

### Claim 17 (depends on 6)

The method of claim 6 wherein said cancer cells are head and neck cancer cells and said tumor peptide is the MAGE-1 or MAGE-3 proteins.

### Claim 18 (depends on 6)

The method of claim 6 wherein said cancer cells are lung cancer cells and said tumor peptide is selected from the group consisting of: Aw68, HER-2/neu, MAGE, GAGE, and BAGE proteins.

### Claim 19 (depends on 6)

The method of claim 6 wherein said cancer cells are prostate cancer cells and said tumor peptide is selected from the group consisting of: HLA-A2, PSA-1, and PSA-3.

### Claim 20 (depends on 6)

The method of claim 6 wherein said cancer cells are Ovarian cancer cells and said tumor peptide is CarcinoEmbryonic Antigen (CEA) or HER-2/neu.

### Claim 21 (depends on 6)

The method of claim 6 wherein said cancer cells are Pancreatic cancer cells and said tumor peptide is CarcinoEmbryonic Antigen (CEA) or HER-2/neu.

### Claim 22 (depends on 6)

The method of claim 6 wherein said cancer cells are Renal cell carcinoma cells and said tumor peptide is MAGE and GAGE proteins.

### Claim 23 (depends on 6)

The method of claim 6 wherein said cancer cells are Uterine cancer cells and said tumor peptide is CarcinoEmbryonic Antigen (CEA) or HER-2/neu.

### Claim 24 (depends on 6)

The method of claim 6 wherein said tumor peptide is p53 or telomerase.

### Claim 25 (depends on 24)

The method of claim 24 wherein said cancer cells are nasopharyngeal carcinoma cells and said tumor peptide is a peptide from EBV.

### Claim 26 (depends on 11)

The method of claim 11 wherein said tumor peptide is p53 or telomerase.

### Claim 27 (depends on 11)

The method of claim 11 wherein said cancer cells are Leukemia and Lymphoma cells and said tumor peptide is selected form the group consisting of: N-ras, K-ras, HTLV-1 proteins, HTLV-2 proteins, and EBV viral proteins.

### Claim 28 (depends on 27)

The method of claim 27 wherein said Leukemia cells are Chronic Myelogenous Leukemia and Acute Myeloid Leukemia cells and said tumor peptide is N-ras or K-ras.

### Claim 29 (depends on 27)

The method of claim 27 wherein said Leukemia cells are T-cell Leukemia cells and said tumor peptide is a peptide from HTLV-I or HTLV-II.

### Claim 30 (depends on 27)

The method of claim 27 wherein said lymphoma cells are non-Hodgkins lymphoma cells and said tumor peptide is a peptide from EBV.