Navigation Links
Researchers generate immunity against tumor vessel protein
Date:4/25/2014

PHILADELPHIA - Sometimes a full-on assault isn't the best approach when dealing with a powerful enemy. A more effective approach, in the long run, may be to target the support system replenishing the supplies that keep your foe strong and ready for battle. A group of researchers from the Abramson Cancer Center and the Perelman School of Medicine at the University of Pennsylvania is pursuing this strategy by employing a novel DNA vaccine to kill cancer, not by attacking tumor cells, but targeting the blood vessels that keep them alive. The vaccine also indirectly creates an immune response to the tumor itself, amplifying the attack by a phenomenon called epitope spreading. The results of the study were published this month in the Journal of Clinical Investigation.

Previous studies have targeted tumor angiogenesis (the formation of new blood vessels that feed the tumor cells). However, this approach can also interfere with normal processes involved in wound healing and development. Penn researchers avoided this pitfall by designing a DNA vaccine that specifically targets TEM1 (tumor endothelial marker 1), a protein that is overexpressed in tumors and poorly expressed in normal tissues.

"We demonstrated that by targeting TEM1, our vaccine can decrease tumor vascularization, increase hypoxia of the tumor and reduce tumor growth," says Andrea Facciabene, PhD, research assistant professor of Obstetrics and Gynecology and a faculty member in the Ovarian Cancer Research Center at Penn Medicine. "Our results confirm that we were directly targeting the tumor vasculature and also indirectly killing tumor cells through epitope spreading."

The Penn team injected mice with a DNA fusion vaccine called TEM1-TT, created by fusing TEM1 complementary DNA with a fragment of the tetanus toxoid (TT). In mouse models of three cancer types (breast, colon, and cervical), tumor formation was delayed or prevented in mice vaccinated with the TEM1-TT DNA vaccine. Specifically, they found that the mouse tumors had suppressed growth, decreased tumor vessel formation, and increased infiltration of immune cells into tumors.

The researchers found that the DNA vaccine, after killing the endothelial cells that make up the tumor vessels (vasculature), also resulted in epitope spreading, meaning that the immune cells of the mice gathered pieces of dead tumor cells (due to hypoxia) to create a secondary immune response against the tumor itself. The vaccine induced specific T cells to fight other tumor cells expression other proteins, in addition to TEM1, thus increasing its therapeutic efficacy.

The new DNA vaccine approach to fight cancer is showing great potential compared to previous studies that focused on tumor cells rather than the blood vessels that allow tumor cells to thrive.

"Until now there have been a lot of clinical trials using DNA vaccines to target tumors themselves, but unfortunately the results have been disappointing," Facciabene notes. "This is a different approach which should heighten optimism for cancer vaccines in general. Moreover, based on what we've seen in our mouse studies, this vaccine doesn't seem to show any significant side effects."

The prevalence of TEM1 in a wide range of tumor types coupled with its scarcity in normal vessels makes it a suitable target both for a prophylactic defense against cancer and a complement to other therapies such as radiotherapy and chemotherapy. "Using this vaccine simultaneously with radiation may eventually have a double synergy," Facciabene says. "Both treatments affect the tumor endothelium, radiotherapy could help the phenomenon of epitope spreading induced by the TEM1-TT vaccine." In addition to ongoing pre-clinical work with human TEM1, Facciabene and colleagues are planning to move on to Phase I human clinical trials.

The authors suggest that TEM1 may also be an excellent target as a prophylactic cancer vaccine for individuals that have a high risk of developing ovarian cancer, such as carriers of the BRCA1/2 mutations, predominant in breast and ovarian cancer. Research to develop those types of strategies is a key goal of Penn's Basser Research Center for BRCA. As a bonafide vaccine, TEM-TT DNA vaccine generates a memory immune response, which Facciabene says is an ideal attribute for high risk populations.


'/>"/>
Contact: Katie Delach
katie.delach@uphs.upenn.edu
215-776-6063
University of Pennsylvania School of Medicine
Source:Eurekalert

Related medicine news :

1. Researchers at LSTM part of the international team to sequence the tsetse genome
2. Oxygen diminishes the hearts ability to regenerate, researchers discover
3. Finnish team of researchers finds a mutation in a tumor of the jaw
4. Depressed? Researchers identify new anti-depressant mechanisms, therapeutic approaches
5. Life stressors trigger neurological disorders, researchers find
6. Penn researchers find link between sleep and immune function in fruit flies
7. Penn Medicine researchers uncover hints of a novel mechanism behind general anesthetic action
8. CU researchers discover target for treating dengue fever
9. BUSM researchers find anti-seizure drug may reduce alcohol consumption
10. Researchers identify children with emotional behavior difficulties
11. Researchers identify similarities between HIV/AIDS and opioid addiction epidemics
Post Your Comments:
*Name:
*Comment:
*Email:
(Date:10/13/2017)... ... , ... Many families have long-term insurance that covers care for a family ... for care if the client has a cognitive impairment diagnosis. , “What this ... often waived, so the benefits from their insurance start immediately,” said Mechell Vieira, owner ...
(Date:10/13/2017)... ... October 13, 2017 , ... Yisrayl Hawkins, Pastor and Overseer ... one of the most popular and least understood books in the Holy Scriptures, Revelation. ... descriptions that have baffled scholars for centuries. Many have tossed it off as mere ...
(Date:10/13/2017)... ... 2017 , ... “America On The Brink”: the Christian history of the United ... the creation of published author, William Nowers. Captain Nowers and his wife, Millie, ... spent thirty years in the Navy. Following his career as a naval aviator ...
(Date:10/12/2017)... ... October 12, 2017 , ... The company has ... today’s consumer and regulatory authorities worldwide. From Children’s to Adults 50+, every formula ... the highest standard. , These products are also: Gluten Free, Non-GMO, Vegan, ...
(Date:10/12/2017)... ... October 12, 2017 , ... Information about the ... to develop to enable prevention of a major side effect of chemotherapy in ... in pediatric patients. For cisplatin, hearing loss is FDA listed on-label as a ...
Breaking Medicine News(10 mins):
(Date:9/27/2017)... for their devotion to personalized service, SMP Pharmacy Solutions announces ... the South Florida Business Journal,s 50 Fastest-Growing Companies, and listed ... national specialty pharmacy has found its niche.  To that end, ... honored by SFBJ as the 2017 Power Leader in Health ... his award in October, Bardisa said of the three achievements, ...
(Date:9/22/2017)... Sept. 22, 2017  As the latest Obamacare repeal ... Bill Cassidy (R-LA) and Lindsey Graham ... the medical device industry is in an odd place. ... the 2.3% excise tax on medical device sales passed ... want covered patients, increased visits and hospital customers with ...
(Date:9/18/2017)... PROVIDENCE, R.I. , Sept. 18, 2017 ... in the fields of bioinformatics and immune ... to develop a protective avian influenza A (H7N9) vaccine. ... is distantly related to seasonal influenza and ... approaches, which rely on prior exposure to be ...
Breaking Medicine Technology: