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

Inovio Pharmaceuticals' Potent hTERT DNA Cancer Vaccine Shows Potential to Reduce Tumors and Prevent Tumor Recurrence

Published: Thursday, July 25, 2013
Last Updated: Thursday, July 25, 2013
Bookmark and Share
Mice and monkey study demonstrates robust and broad immune responses.

Inovio Pharmaceuticals, Inc. announced that in a preclinical study with two animal models, Inovio's hTERT (human telomerase reverse transcriptase) DNA cancer vaccine administered with Inovio's CELLECTRA® adaptive electroporation delivery technology generated robust and broad immune responses, broke the immune system's tolerance to its self-antigens, induced T-cells with a tumor-killing function, and increased the rate of survival. Because high levels of hTERT expression are found in 85% of human cancers, regardless of type, Inovio's cancer candidate holds the potential to perform as a "universal" cancer therapeutic based on these early but unprecedented results. Following this strong preclinical data, Inovio plans to advance its synthetic hTERT cancer vaccine, INO-1400, into clinical trials in 2014.

These results appear in the American Association for Cancer Research journal, Cancer Immunology Research, in a paper entitled: "Highly optimized DNA vaccine targeting human telomerase reverse transcriptase stimulates potent antitumor immunity," authored by Inovio researchers and collaborators.

Dr. J. Joseph Kim, Inovio's president and CEO, said: "Inovio has demonstrated in multiple published human studies that our synthetically optimized DNA vaccines delivered with our CELLECTRA delivery system generate best-in-class T-cell immune responses. Here we show that in monkeys our hTERT DNA cancer vaccine generated T-cell immune responses more than 18-fold higher than the previous best results of a peer's hTERT therapeutic vaccine, which was also a DNA vaccine delivered with electroporation. We are particularly enthusiastic about our vaccine's potential use as a "universal" cancer therapeutic, given that hTERT is present in the vast majority of cancer types yet rare in normal cells. We plan to develop INO-1400 to treat breast and lung cancers and then expand to other cancer types. This hTERT therapy adds to a growing Inovio oncology franchise spearheaded by our phase II candidate, VGX-3100 for treating HPV-related pre-cancers and cancers, as well as our near clinical INO-5150 to treat prostate cancer."

Data from both murine and human systems over the past 10 years have demonstrated that TERT-specific cytotoxic T-lymphocytes (CTLs) can recognize and kill TERT-expressing tumor cells in multiple types of cancers. In fact, previous research has shown that breast cancer patients who mounted an hTERT-specific CTL response exhibited significantly longer rates of survival. However, the immune system's tolerance of cancer cells and their associated antigens produced in the body, which exists to prevent autoimmune diseases, often restricts the immune system's antitumor response. A major challenge for cancer vaccine development has been to develop approaches to break this tolerance in tumor-bearing hosts. Recent advances in our understanding of antigen presentation and tolerance have led Inovio to create this synthetic DNA vaccine targeting the hTERT antigen.

Inovio constructed a highly optimized synthetic DNA vaccine with multiple proprietary features. Using its novel consensus design approach, two differentiating mutations were incorporated in the vaccine sequence to assist T-cells to more readily recognize self-made hTERT antigens and kill the cancer cells to which these antigens are attached (i.e. break tolerance). In addition, Inovio's use of a full length antigen DNA sequence encompasses multiple epitopes (parts of an antigen that are recognized by the immune system), potentially helping the immune system by providing multiple opportunities to overcome a tumor's ability to evade recognition by T-cells.

In the study, Inovio researchers confirmed that vaccination with Inovio's DNA vaccine delivered by adaptive electroporation induced hTERT-specific cellular immune responses with significantly greater T-cell magnitude compared to prior non-Inovio studies. Over four vaccinations there was a significant dose response, showing the value of multiple vaccinations to increase the immune response and highlighting the limitation of alternative technologies that are not amenable to multiple vaccinations such as viral vectors. Vaccination elicited multiple epitopes not only in mice, but also in monkeys, indicating a broad vaccine-induced immune response.

Study results showed that mice vaccinated with Inovio's DNA cancer vaccine and then challenged with a cancerous tumor experienced delayed tumor growth and longer overall survival compared with non-vaccinated mice. Mice first challenged with a tumor and then treated with the hTERT DNA vaccine displayed killing activity of the targeted cancer cells expressing the hTERT antigen, with no killing of normal cells that did not express the hTERT antigen. The treated mice experienced significantly smaller tumors and also longer overall survival. Vaccinated animal results were compared to a control group of animals that did not receive Inovio's DNA cancer vaccine.

In monkeys, whose TERT is 96% similar to human TERT and therefore a highly relevant model for immunotherapeutic vaccine development, the hTERT DNA vaccine elicited strong and broad TERT-specific immune responses and demonstrated the potential to eliminate tumor cells.

Overall, in these studies researchers observed that administration of a synthetic highly optimized hTERT DNA vaccine delivered with electroporation was capable of breaking immune tolerance, and eliciting robust and diverse antigen-specific CTLs, which are responsible for clearing cancerous cells, as well as a potent antitumor response. A favorable safety profile emerged from this study, showing that the vaccine-induced CTLs appeared not to be associated with any major toxicities or organ damage.

The expression of hTERT is thought to correlate with tumor survival and hTERT is associated with 85% of human tumors. Furthermore, there is growing recognition that it may be necessary to target stem cells that produce cancerous cells and recent studies have suggested that cancer stem or stem-like cells also express hTERT. These factors highlight the importance of an effective hTERT-targeting vaccine/immunotherapy and point to the potential benefit of Inovio's novel cancer vaccine.


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 2,400+ 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

Inovio Pharmaceuticals & U.S. Army Receive $3.5 Million Biodefense Grant
Inovio to advance painless device to simultaneously deliver multiple vaccines using electroporation technology.
Thursday, April 11, 2013
Scientific News
RNAi Screening Trends
Understand current trends and learn which application areas are expected to gain in popularity over the next few years.
New Material Opens Possibilities for Super-Long-Acting Pills
A pH-responsive polymer gel could create swallow able devices, including capsules for ultra-long drug delivery.
New Tool For Investigating RNA Gone Awry
A new technology – called “Sticky-flares” – developed by nanomedicine experts at Northwestern University offers the first real-time method to track and observe the dynamics of RNA distribution as it is transported inside living cells.
Access Denied: Leukemia Thwarted by Cutting Off Link to Environmental Support
A new study reveals a protein’s critical – and previously unknown -- role in the development and progression of acute myeloid leukemia (AML), a fast-growing and extremely difficult-to-treat blood cancer.
New Weapon in the Fight Against Blood Cancer
This strategy, which uses patients’ own immune cells, genetically engineered to target tumors, has shown significant success against multiple myeloma, a cancer of the plasma cells that is largely incurable.
TOPLESS Plants Provide Clues to Human Molecular Interactions
Scientists at Van Andel Research Institute have revealed an important molecular mechanism in plants that has significant similarities to certain signaling mechanisms in humans, which are closely linked to early embryonic development and to diseases such as cancer.
Toxin from Salmonid Fish has Potential to Treat Cancer
Researchers from the University of Freiburg decode molecular mechanism of fish pathogen.
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.
Long-sought Discovery Fills in Missing Details of Cell 'Switchboard'
A biomedical breakthrough reveals never-before-seen details of the human body’s cellular switchboard that regulates sensory and hormonal responses.
Tracking Breast Cancer Before it Grows
A team of scientists led by University of Saskatchewan researcher Saroj Kumar is using cutting-edge Canadian Light Source techniques to screen and treat breast cancer at its earliest changes.
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
2,400+ scientific and medical posters
A library of 2,500+ scientific videos on LabTube
3,700+ scientific videos
Close
Premium CrownJOIN TECHNOLOGY NETWORKS PREMIUM FREE!