Corporate Banner
Satellite Banner
Immunology
Scientific Community
 
Become a Member | Sign in
Home>News>This Article
  News
Return

New Target for Lung Cancer Treatment

Published: Tuesday, November 06, 2012
Last Updated: Tuesday, November 06, 2012
Bookmark and Share
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.

"Lung cancer 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 cell adhesion molecule, which is a protein located on the surface of a cell. Its function is to bind with other cells or with the extracellular matrix, the non-cellular environment 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 non-Hodgkin's lymphoma, a disease that usually involves an abnormal proliferation of B cells. 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 target antigen, 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 cancer cells, 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 mouse model 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 lung cancer cells and is a target for antibody-based therapy."

Other study authors from UC Davis are Jason Kato, Chengyi Xiong, Yunpeng Ma and David Gandara. Additional authors are David Pearson from the California Northstate University College of Pharmacy in Rancho Cordova, and Laura Newell of Oregon Health and Science University in Portland.

The study was funded almost entirely by private donations and by the deLeuze Family Endowment for a Non-Toxic Cure for Lymphoma.


Further Information
Access to this exclusive content is for Technology Networks Premium members only.

Join Technology Networks Premium for free access to:

  • Exclusive articles
  • Presentations from international conferences
  • Over 2,500+ scientific posters on ePosters
  • More than 3,700+ scientific videos on LabTube
  • 35 community eNewsletters


Sign In



Forgotten your details? Click Here
If you are not a member you can join here

*Please note: By logging into TechnologyNetworks.com you agree to accept the use of cookies. To find out more about the cookies we use and how to delete them, see our privacy policy.

Related Content

Scientists Create CRISPR/Cas9 Knock-In Mutations in Human T Cells
In a project spearheaded by investigators at UC San Francisco, scientists have devised a new strategy to precisely modify human T cells using the genome-editing system known as CRISPR/Cas9.
Tuesday, July 28, 2015
Engineers Crack DNA Code of Autoimmune Disorders
Researchers have identified an unexpectedly general set of rules that determine which molecules can cause the immune system to become vulnerable to the autoimmune disorders lupus and psoriasis.
Wednesday, June 10, 2015
Using microRNA Fit to a T (Cell)
Researchers show B cells can deliver potentially therapeutic bits of modified RNA.
Friday, November 29, 2013
Autoimmune Disease Strategy Emerges from Immune Cell Discovery
UCSF experiments halt pancreas destruction in mouse model of diabetes.
Wednesday, September 11, 2013
Tuberculosis and Parkinson’s Disease Linked by Unique Protein
UCSF researchers seek way to boost protein to fight both diseases.
Wednesday, September 11, 2013
Therapy Could Treat Breast Cancer that's Spread to Brain
Researchers have successfully combined cellular therapy and gene therapy in a mouse-model system to develop a viable treatment strategy for breast cancer that has spread to a patient's brain.
Tuesday, August 06, 2013
Immune System Molecule Promotes Tumor Resistance
A team of scientists has shown for the first time that a signaling protein involved in inflammation also promotes tumor resistance to anti-angiogenic therapy.
Tuesday, August 06, 2013
Intestinal Bacteria May Fuel Inflammation and Worsen HIV Disease
Changes in intestinal bacteria may help explain why successfully treated HIV patients still experience life-shortening chronic diseases.
Friday, July 12, 2013
Prenatal Maternal Antibodies Affect Child Development
Prenatal exposure to specific combinations of antibodies found only in mothers of children with autism leads to changes in the brain that adversely affect behavior and development.
Wednesday, July 10, 2013
Absence of Gene Leads to Earlier, More Severe Case of Multiple Sclerosis
UCSF finding in animal study may lead to biomarker that predicts course of disease in humans.
Tuesday, June 25, 2013
Developmental Protein Plays Role in Spread of Cancer
A protein used by embryo cells during early development, and recently found in many different types of cancer, apparently serves as a switch regulating metastasis.
Tuesday, June 18, 2013
Depression Linked to Telomere Enzyme, Aging, Chronic Disease
The first symptoms of major depression may be behavioral, but the common mental illness is based in biology — and not limited to the brain.
Thursday, May 23, 2013
Program for Breakthrough Biomedical Research to Celebrate 15 Years
A program that fosters basic science projects of potentially high impact is celebrating 15 years of discovery at UC San Francisco.
Tuesday, May 21, 2013
UCSF Scientists Use Human Stem Cells to Generate Immune System in Mice
Raising hopes for cell-based therapies, UC San Francisco researchers have created the first functioning human thymus tissue from embryonic stem cells in the laboratory.
Friday, May 17, 2013
Tumor-Activated Protein Promotes Cancer Spread
Researchers report that cancers physically alter cells in the lymphatic system to promote the spread of disease.
Tuesday, May 14, 2013
Scientific News
Inciting an Immune Attack on Cancer Cells
A new minimally invasive vaccine that combines cancer cells and immune-enhancing factors could be used clinically to launch a destructive attack on tumors.
Inflammation Linked to Colon Cancer Metastasis
A new Arizona State University research study led by Biodesign Institute executive director Raymond DuBois has identified for the first time the details of how inflammation triggers colon cancer cells to spread to other organs, or metastasize.
New Strategy for Combating Adenoviruses
Using an animal model they developed, Saint Louis University and Utah State university researchers have identified a strategy that could keep a common group of viruses called adenoviruses from replicating and causing sickness in humans.
Major Advance Toward More Effective, Long-Lasting Flu Vaccine
Collaboration shows vaccine candidate can produce powerful ‘broadly neutralizing antibodies’ in animal models.
Immune System: Help for Killer Cells
A study from the University of Bonn may show the way to more effective vaccines.
Protein Found to Control Inflammatory Response
A new Northwestern Medicine study shows that a protein called POP1 prevents severe inflammation and, potentially, diseases caused by excessive inflammatory responses.
A Leap Forward in Vaccinating Against HIV
A team of scientists has developed an experimental vaccine candidate that successfully stimulates the immune system activity in animal models necessary to stop HIV infection.
MRI Scanners Can Steer Therapeutics to Specific Target Sites
Scientists from the University of Sheffield have discovered MRI scanners, normally used to produce images, can steer cell-based, tumour busting therapies to specific target sites in the body.
Agricultural Intervention Improves HIV Outcomes
A multifaceted farming intervention can reduce food insecurity while improving HIV outcomes in patients in Kenya, according to a randomized, controlled trial led by researchers at UC San Francisco.
Team Finds Early Inflammatory Response Paralyzes T Cells
Findings could have enormous implications for immunotherapy, autoimmune disorders, transplants and other aspects of immunity.
SELECTBIO

Skyscraper Banner
Go to LabTube
Go to eposters
 
Access to the latest scientific news
Exclusive articles
Upload and share your posters on ePosters
Latest presentations and webinars
View a library of 1,800+ scientific and medical posters
2,500+ scientific and medical posters
A library of 2,500+ scientific videos on LabTube
3,700+ scientific videos
Close
Premium CrownJOIN TECHNOLOGY NETWORKS PREMIUM FREE!