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Arthritis Issues Author: Staff Editor Last Updated: Feb 14, 2018 - 9:41:02 AM



Rush Testing Potential Rheumatoid Arthritis Vaccine

By Staff Editor
Feb 14, 2018 - 9:36:29 AM



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(HealthNewsDigest.com) - Rheumatoid arthritis affects about 1.3 million people in the United States, and the standard treatments don’t work in more than half of RA patients. The treatments also increase the risk of infection and are very expensive.

In the hope of offering a better alternative, an NIH-funded collaboration between researchers at Rush University Medical Center and a biotechnology company is testing a vaccine for RA that has been found effective in preliminary laboratory studies. If successful, the researchers could move on to a clinical trial of the vaccine in three or four years.

RA is an autoimmune disease — a condition in which the disease-fighting immune system mistakenly attacks and inflames healthy tissue. It mainly affects the inner linings of the joints and can lead to chronic pain, joint deformity and disability.

The current treatments for RA either block the immune cells that cause the disease’s inflammatory tissue destruction or suppress the immune system in general. “Our vaccine instead targets the immune cells that trigger and maintain the disease process,” says Katalin Mikecz, MD, PhD, professor of orthopedic surgery, who is leading the study of the vaccine at Rush.

“This approach means that our vaccine is safer than current therapies because it does not target cells that protect the body from infections. Since the vaccine is composed of synthetic peptides, it also is less expensive than biologics (current treatments derived from biological sources).”

Taking a LEAPS forward

CEL-Sci, a biotechnology company based in Vienna, Virginia, developed the vaccine in collaboration with Mikecz and her colleagues at Rush.  The vaccine employs what’s called a ligand epitope antigen presentation system, or LEAPS for short.

Ligands, epitopes and antigens are types of molecules. Depending on the particular composition of each one, they can belong to either of the larger categories of molecules known as peptides or proteins. For the LEAPS vaccine, they work in the following way:

  • An antigen is usually a foreign substance that attracts the immune system’s attention and prompts its response. In RA, the immune system mistakenly reacts to a protein found in the cartilage tissue of the joints.
  • Epitopes are small stretches of the antigen to which immune cells react. In RA, white blood cells known as T lymphocytes recognize these epitopes and make inflammatory molecules (called cytokines). The T lymphocytes also instruct other immune cells to make antibodies against the epitopes. Together, the cytokines and serum antibodies responding to cartilage antigens (or their epitopes) can attack and destroy the joints.
  • Ligands bind with other molecules, which usually are on the surface of immune cells or other cells. In the LEAPS vaccine, the ligand specifically targets and binds to T lymphocytes, but instead of prompting an inflammatory response from them, the vaccine causes T lymphocytes to calm down.

Vaccine found effective in laboratory mice

In a study of laboratory mice that had been induced with an RA-like disease, researchers at Rush and Cel-Sci found that the vaccine stopped the disease’s destruction of joint tissues. The research team published the results of the study last year in the journal Vaccine.

“Our results indicated that both the composition and output of inflammatory factors changed in the immune cells (particularly in T lymphocytes) of the mice after they were given the LEAPS vaccine,” Mikecz says. Based on these results, the National Institute of Arthritis and Musculoskeletal and Skin Diseases (part of the National Institutes of Health) awarded the researchers a $1.5 million grant to study the vaccine further.

“We know the vaccine modulates the immune system so that the cells don’t turn against the joints, but we don’t know exactly how it happens,” Mikecz says. “In the current phase of the project, we’ll further investigate the exact molecular events and pathways involved in these changes at the single cell level.”

The researchers will examine those molecular mechanisms first in mouse cells and then in cells of donated human blood. “We expect to see similar reductions in the inflammatory responses of mouse and human cells in the presence of the vaccine,” Mikecz says.

They also will conduct tests to determine the vaccine’s safety. “These kinds of studies are necessary in order to obtain FDA approval for human use,” Mikecz says.

Key component was a result of ‘unexpected fortunate discoveries’

In addition, the researchers plan to add another epitope peptide to the vaccine in the hope of strengthening it. The original vaccine uses a peptide epitope known as PG70, which Mikecz and her colleagues identified in mice with arthritis that was induced using a protein called cartilage PG antigen. (This model of RA is known as PG-induced arthritis.) The animal model was discovered in the 1980s at McGill University in Montreal, where Mikecz was a postdoctoral fellow studying human cartilage structure and molecular composition.

She and other researchers then discovered that cartilage epitopes such as PG70 also were recognized by immune cells and antibodies from RA patients. “These were unexpected, fortunate discoveries,” she says.

Cel-Sci originally sought out the Rush researchers for the model of RA in laboratory mice they’ve developed, which isn’t commercially available. When company’s scientist Daniel Zimmerman, PhD and Mikecz’s team met, they seized on the idea of adding PG70 to Cel-Sci’s existing LEAPS vaccine platform.

If the studies are successful and the vaccine receives FDA approval, the researchers will advance it to clinical trials in patients with RA. Mikecz hopes to begin these trials in the next three to four years.

“Right now, there isn’t anything like it used for rheumatoid arthritis therapy,” she says. “This vaccine would be a new kind of approach to quiet the immune system.”



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