Researchers one step closer to elusive cancer vaccine

October 29, 2007

When cells become cancerous, the sugars on their surfaces undergo distinct changes that set them apart from healthy cells. For decades, scientists have tried to exploit these differences by training the immune system to attack cancerous cells before they can spread and ravage the body.

Now, researchers at the University of Georgia Cancer Center have synthesized a carbohydrate-based vaccine that – in mice – has successfully triggered a strong immune response to cancer cells. The finding, published in the October issue of the journal Nature Chemical Biology, brings the scientists one step closer to a much-sought-after “cancer vaccine.”

“In mice we can elicit very strong antibody responses and we have shown that the antibody responses are functional – that they can kill cancer cells,” said lead author Geert-Jan Boons, Franklin professor of chemistry.

Vaccines are currently use to prevent diseases by priming the immune system to recognize and attack a virus or bacteria. The vaccine that Boons and his team have developed, on the other hand, is a therapeutic vaccine that trains the body’s immune system to fight an existing disease.

The discovery in the 1970s of unique sugars on cancer cells set scientists in search of a way to get the immune system to recognize and attack cells that express these cancer-associated sugars. Until now, however, the results have been less than spectacular.

Cancer cells originate in the body, and the immune system leaves them alone because it distinguishes between the body’s own cells and foreign invaders such as viruses and bacteria.

Boons explained that early cancer vaccines were created by linking the tumor-associated carbohydrate with a foreign protein. The immune system, perhaps not surprisingly, attacked the protein and the linker molecules, but generally left the carbohydrate alone.

“We needed to come up with a vaccine that does not give our immune system a chance to go after anything else but the tumor-associated carbohydrate,” Boons said. “In other words, there should no junk that can induce an immune response to something other than the tumor-associated carbohydrate.”

Rather than using naturally derived and purified proteins and linkers, Boons and his team created a vaccine synthetically from scratch by stacking molecules together and arranging them in the appropriate configuration. In 2005, they created a fully synthetic vaccine that stimulated an immune response to the tumor-associated carbohydrate alone. The vaccine stimulated only low antibody levels, however, so the researchers began optimizing the components of the vaccine to illicit a stronger immune response.

Their optimized vaccine includes a tumor-associated carbohydrate that triggers the immune system’s B cells, a part of a protein that triggers the immune system’s T cells and a linker molecule that stimulates the production of generalized immune components known as cytokines.

The results of their three-pronged approach were astounding, particularly with respect to a critical component of the immune system known as IgG.

“When we tested our best vaccine we got really, really fabulous antibody levels that have never been seen before,” Boons said. “The levels of IgG antibody production were 100 times better than with conventional approaches.”

The vaccine has been successful in creating an antibody response that can kill cultured epithelial cells – those commonly involved in most solid tumors, such as breast and colorectal cancer – derived from mice and in stimulating an immune response in healthy mice. The researchers are currently testing the vaccine in mice with cancer, and Boons hopes to start phase I clinical trials in humans within a year.

Despite his enthusiasm for his work, Boons cautions that it’s too early to predict how the vaccine will perform in humans.

“There’s a very big step going from mice to humans,” he said. “Other cancer vaccines have worked in mice but not in humans.”

In addition to testing the new vaccine, Boon’s team is exploring the specific components of the immune response as they relate to cancer, determining the exact cytokines and antibodies that are most effective against cancer cells.

“We’re looking at which molecules are being upregulated at each level of immune response,” Boons said. “That gives us a road map to further optimize each component of the vaccine.”

Source: University of Georgia

Explore further: Flu infection study increases understanding of natural immunity

Related Stories

Flu infection study increases understanding of natural immunity

January 23, 2018
People with higher levels of antibodies against the stem portion of the influenza virus hemagglutinin (HA) protein have less viral shedding when they get the flu, but do not have fewer or less severe signs of illness, according ...

Boosting cancer therapy with cross-dressed immune cells

January 22, 2018
Researchers at EPFL have created artificial molecules that can help the immune system to recognize and attack cancer tumors. The study is published in Nature Methods.

Improving vaccines for the elderly by blocking inflammation

January 22, 2018
By identifying why skin immunity declines in old age, a UCL-led research team has found that an anti-inflammatory pill could help make vaccines more effective for elderly people.

Firm advances human trials of revolutionary vaccine

January 18, 2018
Amid predictions that this year's flu vaccine will offer limited protection, medical researchers are renewing their focus on a universal flu vaccine.

Novel genomic tools provide new insight into human immune system

January 19, 2018
When the body is under attack from pathogens, the immune system marshals a diverse collection of immune cells to work together in a tightly orchestrated process and defend the host against the intruders. For many decades, ...

Creation of synthetic horsepox virus could lead to more effective smallpox vaccine

January 19, 2018
UAlberta researchers created a new synthetic virus that could lead to the development of a more effective vaccine against smallpox. The discovery demonstrates how techniques based on the use of synthetic DNA can be used to ...

Recommended for you

New approach attacks 'undruggable' cancers from the outside in

January 23, 2018
Cancer researchers have made great strides in developing targeted therapies that treat the specific genetic mutations underlying a patient's cancer. However, many of the most common cancer-causing genes are so central to ...

Study: Cells of three advanced cancers die with drug-like compounds that reverse chemo failure

January 23, 2018
Researchers at Southern Methodist University have discovered three drug-like compounds that successfully reverse chemotherapy failure in three of the most commonly aggressive cancers—ovarian, prostate and breast.

'Hijacker' drives cancer in some patients with high-risk neuroblastoma

January 23, 2018
Researchers have identified mechanisms that drive about 10 percent of high-risk neuroblastoma cases and have used a new approach to show how the cancer genome "hijacks" DNA that regulates other genes. The resulting insights ...

Enzyme inhibitor combined with chemotherapy delays glioblastoma growth

January 23, 2018
In animal experiments, a human-derived glioblastoma significantly regressed when treated with the combination of an experimental enzyme inhibitor and the standard glioblastoma chemotherapy drug, temozolomide.

Researchers identify a protein that keeps metastatic breast cancer cells dormant

January 23, 2018
A study headed by ICREA researcher Roger Gomis at the Institute for Research in Biomedicine (IRB Barcelona) has identified the genes involved in the latent asymptomatic state of breast cancer metastases. The work sheds light ...

Workouts may boost life span after breast cancer

January 22, 2018
(HealthDay)—Longer survival after breast cancer may be as simple as staying fit, new research shows.

1 comment

Adjust slider to filter visible comments by rank

Display comments: newest first

freemind
2 / 5 (1) Oct 29, 2007
That's really really really good news...

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.