Scientists identify new target for lung cancer treatment

November 1, 2012 in Cancer

A team of UC Davis investigators has discovered a protein on the surface of lung cancer cells that could prove to be an important new target for anti-cancer therapy. A series of experiments in mice with lung cancer showed that specific targeting of the protein with monoclonal antibodies reduced the size of tumors, lowered the occurrence of metastases and substantially lengthened survival time. The findings will be published in the November issue of Cancer Research.

" continues to be one of the biggest killers in the United States, and very few treatments directly target it," said Joseph Tuscano, co-principal investigator of the study and professor of hematology and oncology in the UC Davis Department of Internal Medicine. "Our findings may ultimately lead to the identification of a novel and specific therapy for lung cancer."

Lung cancer is the most common cause of death from cancer in both men and women in the United States. Despite new treatments, survival from non-small cell types of lung cancer—the most common form of the disease—averages less than one year.

The UC Davis investigation focused on CD22, a , which is a protein located on the surface of a cell. Its function is to bind with other cells or with the , the non- surrounding cells.

The research group has worked on CD22 for many years since finding that B lymphocytes carry CD22, making it a potential target for the treatment of , a disease that usually involves an abnormal proliferation of . They developed a monoclonal antibody—known as HB22.7—to target CD22, and it was found to successfully treat non-Hodgkin's lymphoma in mouse models. HB22.7, as well as other monoclonal antibody-based therapies, have little toxicity because they very specifically home in on and destroy cells containing the , in this case CD22. HB22.7 is currently being prepared for use in human patients in anticipation of clinical trials.

Although the researchers at first thought that CD22 was uniquely expressed on B cells, they discovered serendipitously that it also appears on lung , although not on healthy cells in the lung. The investigators found CD22 in seven of the eight cell lines evaluated, which included the major lung cancer subtypes of adenocarcinoma, squamous cell, bronchoalveolar and carcinoid, but not the epidermoid subtype. The authors also examined publicly available databases and discovered that other lung cancer cell lines also expressed CD22.

"Our observation that CD22 is expressed on lung cancer cells is a very exciting discovery, especially since we already have developed a monoclonal antibody that targets this protein," said Robert O'Donnell, professor of hematology and oncology in the UC Davis Department of Internal Medicine and co-principal investigator of the study. "This could bring about a new treatment for a disease that badly needs a new therapeutic approach."

Investigators next tested the effect of treating experimental mouse models of lung cancer with HB22.7. They first implanted tumor cells in the lung, and after the tumors reached a specific size, the mice were given four weekly treatments of either HB22.7 or a placebo. Tumors in the mice treated with HB22.7 grew to only about half the size of those in the control mice.

HB22.7 also had positive results in a model that approximated lung-cancer metastasis, involving the ability of circulating cancer cells to implant themselves into an organ (in this case, the lung) and grow a tumor. For these experiments, lung cancer cells were injected into the bloodstream of mice, followed by four weekly treatments of either HB22.7 or a placebo. At the end of treatment, most of the lung tissue from the control group contained a great deal of tumor—in one mouse the entire lung was nearly replaced with cancer. The treated mice had virtually no tumor growth in evidence, and only one had microscopic evidence of a single lung tumor.

Furthermore, mice treated with HB22.7 had significantly longer survival: more than 90 percent were still alive at the end of the 84-day trial, while most of the untreated mice had died by the 14th day, and all of them had died by day 40.

"The results of the metastasis experiments were really dramatic," said Tuscano. "They indicate that CD22 may play a significant role in the development of lung-cancer metastasis."

Interestingly, when HB22.7 was tested in a inoculated with a cell line found to be resistant to HB22.7 when tested in cell culture, tumor growth was also significantly reduced compared to tumors in control mice. According to the authors, the reason for this is unclear, but they suspect that CD22 may have other immunological properties in a living animal, which are not evident in tissue culture.

The research group is currently "humanizing" the monoclonal antibody HB22.7 in anticipation of clinical trials. This involves modifying the protein sequences to make the antibody—which was derived from mice—to be more similar to natural antibodies produced by humans.

Because they know that HB22.7 homes in on cancer cells, they also are exploring the use of HB22.7 as a vehicle to deliver drugs to lung cancer, which may make current drug therapy more effective. The article is titled "The CD22 antigen is broadly expressed on and is a target for antibody-based therapy."

Journal reference: Cancer Research search and more info website

Provided by UC Davis search and more info website

4 /5 (1 vote)  

Rank 4 /5 (1 vote)
Related Stories
Relevant PhysicsForums posts

More news stories

American cancer society celebrates 100 years of progress

(HealthDay)—The American Cancer Society, which is celebrating on Wednesday a century of fighting a disease once viewed as a death sentence, is making a pledge to put itself out of business.

Cancer created 11 hours ago | popularity not rated yet | comments 0

CT detects twice as many lung cancers as X-ray at initial screening exam

National Lung Screening Trial (NLST) investigators also conclude that the 20 percent reduction in lung cancer mortality with low-dose computed tomography (LDCT) versus chest X-ray (CXR) screening previously reported in the ...

Cancer created 12 hours ago | popularity not rated yet | comments 0

Research offers promising new approach to treatment of lung cancer

Researchers have developed a new drug delivery system that allows inhalation of chemotherapeutic drugs to help treat lung cancer, and in laboratory and animal tests it appears to reduce the systemic damage ...

Cancer created 15 hours ago | popularity not rated yet | comments 0 | with audio podcast

Study details genes that control whether tumors adapt or die when faced with p53 activating drugs

When turned on, the gene p53 turns off cancer. However, when existing drugs boost p53, only a few tumors die – the rest resist the challenge. A study published in the journal Cell Reports shows how: tumors that live even i ...

Cancer created 15 hours ago | popularity not rated yet | comments 0 | with audio podcast

Small increase in cancer risk following CT scans in childhood and adolescence

Study leader, Professor John Mathews from the University of Melbourne said this small increase in cancer risk must be weighed against the undoubted benefits from CT scans in diagnosing and monitoring disease.

Cancer created 20 hours ago | popularity not rated yet | comments 0


Slowing the aging process—only with antibiotics

Swiss scientists reveal the mechanism responsible for aging hidden deep within mitochondria—and dramatically slow it down in worms by administering antibiotics to the young.

Researchers complete largest genetic sequencing study of human disease

Researchers from Queen Mary, University of London have led the largest sequencing study of human disease to date, investigating the genetic basis of six autoimmune diseases.

Brain can be trained in compassion, study shows

Until now, little was scientifically known about the human potential to cultivate compassion—the emotional state of caring for people who are suffering in a way that motivates altruistic behavior.

Rate of bicycle-related fatalities significantly lower in states with helmet laws

Existing research shows that bicyclists who wear helmets have an 88 percent lower risk of brain injury, but researchers at Boston Children's Hospital found that simply having bicycle helmet laws in place showed a 20 percent ...

Having both migraines, depression may mean smaller brain

(HealthDay)—Migraines and depression can each cause a great deal of suffering, but new research indicates the combination of the two may be linked to something else entirely—a smaller brain.

Novel approach for influenza vaccination shows promise in early animal testing

A new approach for immunizing against influenza elicited a more potent immune response and broader protection than the currently licensed seasonal influenza vaccines when tested in mice and ferrets. The vaccine ...