# US 6,534,062 B2 · Methods for increasing a cytotoxic T lymphocyte response in vivo

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- Number: US 6,534,062 B2
- Document ID: US6534062B2
- Status: Granted
- Kind: B2
- Application number: 09/820,484
- Filed: 2001-03-28
- Published: 2002-10-03
- Granted: 2003-03-18
- Earliest claimed: 2000-03-28
- Assignees: The Regents of the University of California; The United States of America as represented by the Department of Veterans Affairs
- Inventors: Eyal Raz; Hearn Jay Cho; Douglas Richman; Anthony A. Horner
- Web page: https://patentgrep.com/patent/US6534062B2

## CPC

- A61K 39/39: characterised by the immunostimulating additives, e.g. chemical adjuvants
- A61K 39/0011: {Cancer antigens}
- A61K 39/12: Viral antigens
- A61K 39/21: Retroviridae, e.g. equine infectious anemia virus
- A61K 39/385: Haptens or antigens, bound to carriers
- A61K 40/10: characterised by the cell type used
- A61K 40/46: Viral antigens
- A61K 2039/53: {DNA (RNA) vaccination}
- A61K 2039/54: {characterised by the route of administration}
- A61K 2039/543: {intranasal}
- A61K 2039/545: {characterised by the dose, timing or administration schedule}
- A61K 2039/55: {characterised by the host/recipient, e.g. newborn with maternal antibodies}
- A61K 2039/55561: {CpG containing adjuvants; Oligonucleotide containing adjuvants}
- A61K 2039/57: {characterised by the type of response, e.g. Th1, Th2}
- A61K 2039/585: {wherein the target is cancer}
- A61K 2039/6025: {Nucleotides}
- C12N 2740/16134: Use of virus or viral component as vaccine, e.g. live-attenuated or inactivated virus, VLP, viral protein
- C12Q 1/703: {Viruses associated with AIDS}
- 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)
- C12N: MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA (microbiological testing media C12Q1/00)
- C12Q: MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS (immunoassay G01N33/53); COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES

## Abstract

The invention provides methods for T helper-independent activation of an antigen-specific cytotoxic T lymphocyte response in an individual. The methods generally involve administering to an individual an immunostimulatory nucleic acid molecule in an amount effective to increase an antigen-specific CTL response in the individual. The invention further provides methods for increasing chemokine secretion, which can block HIV infection.

## Claims

### Claim 1

A method of increasing antigen-specific T lymphocyte activity in a CD4+ T cell-deficient individual, comprising administering a formulation comprising an immunostimulatory nucleic acid molecule and an antigen in an amount effective to increase antigen-specific CTL activity, wherein the immunostimulatory nucleic acid is covalently linked to the antigen.

### Claim 2 (depends on 1)

The method of claim 1, wherein the immunostimulatory nucleic acid comprises the sequence 5′ C-G 3′.

### Claim 3 (depends on 1)

The method of claim 1, wherein the antigen is associated with an intracellular pathogen.

### Claim 4 (depends on 1)

The method of claim 1, wherein the antigen is a tumor-associated antigen.

### Claim 5 (depends on 1)

The method of claim 1, wherein the immunostimulatory nucleic acid molecule comprises a nucleotide sequence selected from the group consisting of 5′-purine-purine-cytosine-guanine-pyrimidine-pyrimidine-3′; 5′-purine-TCG-pyrimidine-pyrimidine-3′; and 5′-(TGC)n-3′, where n≧1.

### Claim 6 (depends on 1)

The method of claim 1, wherein the individual has a reduced number of CD4+ T lymphocytes due to a primary immunodeficiency.

### Claim 7 (depends on 1)

The method of claim 1, wherein the individual has a reduced number of CD4+ T lymphocytes due to an acquired immunodeficiency.

### Claim 8 (depends on 7)

The method of claim 7, wherein the acquired immunodeficiency is a temporary immunodeficiency due to a treatment selected from the group consisting of radiation therapy to treat a cancer, chemotherapy to treat a cancer, immunosuppression following bone marrow transplantation, immunosuppression caused by treatment for an autoimmune disease, and immunosuppression following organ transplantation.

### Claim 9 (depends on 7)

The method of claim 7, wherein the acquired immunodeficiency is acquired immunodeficiency syndrome.

### Claim 10 (depends on 1)

The method of claim 1, wherein said immunostimulatory nucleic acid molecule is administered to a mucosal tissue.

### Claim 11 (depends on 1)

The method of claim 1, wherein said immunostimulatory nucleic acid molecule is administered systemically.