Scientists Report Breakthrough in Developing Vaccines To Treat Chronic HBV Infection and Cancer

[Guest guest]

Scientists Report Breakthrough in Developing Vaccines To Treat Chronic

Infection and Cancer

January 18, 2001

Epimmune and Scripps Researchers Discover How to Overcome Problem of Immune

System Tolerance to Chronic Hepatitis B Virus in Animal Model

SAN DIEGO, Jan. 17 /PRNewswire/ -- Scientists at Epimmune Inc. (Nasdaq:

EPMN) and at The Scripps Research Institute, La Jolla, reported today in the

Journal of Immunology that a new epitope-based vaccine approach can overcome

the problem of immune tolerance to chronic hepatitis B virus in an animal

model. Immune tolerance is a primary barrier to the development of effective

vaccines to treat most chronic infections and cancer.

The published studies were performed using mice that were specially

engineered to carry the complete hepatitis B virus (HBV) genome (HBV

transgenic mice). The livers of these transgenic mice produce large amounts

of viral proteins and infectious virus throughout their life in a manner

similar to humans who are chronically infected with HBV. As a result of the

chronic production of viral proteins, these animals are highly tolerant of

the virus and do not normally mount an anti-HBV immune response, a condition

known as immune tolerance.

" We were looking for a new vaccine approach to activate the immune system

against HBV in immune tolerant mice, " said Chisari, M.D., Head of the

Division of Experimental Pathology at The Scripps Research Institute.

" Previous attempts using vaccines made of whole antigens or DNA encoding

whole antigens were not successful. "

Conventional vaccines consist of the whole pathogen (disease-causing

organism), which has been weakened or killed, or whole antigens. Antigens

are proteins from the pathogen that elicit an immune response. One of the

newest vaccine approaches uses DNA that, when taken up by the cells of the

body, will produce the specified antigens.

" We found that the only vaccine capable of inducing immune responses in the

mice was based on a new approach using small fragments of antigens called

epitopes, " said Dr. Chisari. Epitopes are very short sequences of amino

acids called peptides (the chemical building blocks of proteins) that act

like chemical flags to alert and activate the immune system.

As part of the collaborative work, epitopes from the HBV genome (entire DNA

sequence) were identified using Epimmune's Epitope Identification System

(EIS). Specifically, epitopes were chosen that had amino acid sequences

known to activate cytotoxic T cells (CTLs) of the immune system. The

activation of CTLs is an important immune response because these cells are

capable of directly killing other cells infected with a virus. CTLs also

produce factors that have anti-viral effects, which directly suppress the

virus.

The " CTL epitopes " were then used to immunize the HBV transgenic mice, which

resulted in the induction of CTLs specifically against HBV. In addition, the

CTLs from these mice were shown to have the capacity to decrease HBV virus

production without causing severe liver damage commonly known as hepatitis.

" Immunization of the HBV transgenic mice with CTL epitopes appears to be key

in inducing the CTL response, " said Dr. Chisari. " Our work has now shown

that immunization with epitope-based vaccines can overcome the immune

tolerance established in these animals by the chronic production of HBV

proteins. "

Epimmune is developing epitope-based vaccines to prevent and treat

infectious diseases and cancer. The Company believes that epitopes represent

the most efficient and potent way to, in effect, teach the immune system to

recognize and attack pathogens or cancerous cells. Several types of epitopes

can be packaged together in one vaccine to stimulate different types of T

cells for a potent and directed immune response.

" The ability to use CTL epitopes to break immune tolerance is an important

observation in guiding our epitope-based vaccine program not only for HBV,

but for other chronic viral diseases and cancers, " said Alessandro Sette,

Ph.D., Chief Scientific Officer at Epimmune. " Each disease is different but

all have an element of immune tolerance that must be overcome. Understanding

that immunization with CTL epitopes can break tolerance while whole antigens

do not is important support for our rationale in moving the epitope

technology into clinical trials. "

The study results were reported in a publication entitled " Overcoming T Cell

Tolerance to the Hepatitis B Virus Surface Antigen in HBV Transgenic Mice, "

which appears in the January 15th issue of the Journal of Immunology.

Epimmune Inc. is a leader in using gene maps of cancer-associated proteins

and infectious agents to design vaccines that induce cellular immunity. The

company's extensive technology platform is based on its pioneering work in

deciphering the genetic code which regulates T-cell activation and

identifying antigen fragments known as epitopes which can activate highly

targeted T-cell responses to tumors, viruses, bacteria and parasites. This

new field of pharmacology opens two significant areas of pharmaceutical

development: protective vaccines that activate T-cell protection against

infections, such as HIV and hepatitis C, and therapeutic vaccines designed

to stimulate antigen-specific T-cell responses to infections, such as HIV,

hepatitis C and hepatitis B, and tumors such as breast, colon, lung and

prostate. For more information on Epimmune, visit www.epimmune.com.

This press release includes forward-looking statements that reflect

management's current views of future events. Actual results may differ

materially from the above forward-looking statements due to a number of

important factors, including but not limited to the risks associated with

the Company's ability to develop vaccines using epitopes, the ability of

epitope-based vaccines to control HBV and other infectious diseases, the

safety and efficacy of epitope-based vaccines in humans, the Company's

ability to enter into and maintain new collaborations, achievement of

research and development objectives by the Company and any collaborator, the

timing and cost of conducting human clinical trials, the regulatory approval

process, and the possibility that testing may reveal undesirable and

unintended side effects or other characteristics that may prevent or limit

the commercial use of proposed products. These factors are more fully

discussed in the Company's 1999 Form 10-K, the most recent 10-Qs and other

periodic reports filed with the Securities and Exchange Commission.

SOURCE Epimmune Inc.

CONTACT: F. Keane, VP, Corporate Development of Epimmune Inc.,

858-860-2500; or Hansen of E. Atkins & Associates, 858-860-0266,

for Epimmune Inc.

Web site: http://www.epimmune.com (EPMN)