As it turns out, there are as many kinds of Tregs as there are types of tapas in Granada. But there is only one Tregitope. OK, make that several (in fact, there are six that we aim to use for Tregitope therapy in autoimmune disease). Meanwhile, in Granada, the copas are flowing, and Tregitope is being presented to the >3,000 participants at Autoimmunity 2012. Leslie Cousens, Ph.D. (EpiVax) and David W. Scott, Ph.D. (Vice Chair for Research, Department of Medicine at USUHS), presented “Tregitope mechanism of Action” and “IgG-Derived T Cell Epitopes (Tregitopes) Suppress Immune Responses by Activating nTregs”, respectively, today at 2 PM. David described the effect of Tregitopes in D011.10 FoxP3 transgenic mice (induction of iTregs) and Leslie described the three-step mechanism of action.

Tregitope iTreg induction

Tregitopes were also mentioned by Bruce Mazer, M.D. of McGill University during his talk on the effect of IVIG (induction of regulatory T cells) in asthma. Bruce has demonstrated that the induction of Tregs in asthmatic lungs is equal or better than Treg induction by IVIG, in the OVA-allergy model. Dr. Srini Kaveri Ph.D. (INSERM) has integrated Tregitopes into his presentation on the IVIG mechanism of action; that much was evident on Thursday.

Leslie and Wassim at Autoimmunity 2012

In case you missed these talks, on Sunday, Annie De Groot M.D., EpiVax CEO, will present ” Tregitope applications to tolerance induction in autoimmune diseases” as the opening talk of the Plenary Session. Wassim Elyaman, Ph.D. is also presenting a poster on Tregitope application to Multiple Sclerosis. See here for a great picture of Wassim and Leslie at Wassim’s poster.

Tregitope was also featured at the May 2012 American Association of Immunologists (AAI) meeting, where poster presentations on the topic were “mobbed” according to eyewitnesses. Why the excitement? Because Tregitope truly represents a paradigm shift for autoimmunity and tolerance.

Stay tuned for more news on Tregitope – including Safety and Toxicity studies (scheduled for June, 2012) and proof-of-concept Phase I trials (to be scheduled in 2013). This is a banner year for Tregitopes – click our RSS feed to stay in the loop.

Together, they plan to change the future of vaccine research.

Poznansky, VIC’s founder and director, says the newly formed consortium, called VaxCelerate, is one of a few recently approved DARPA (Defense Advanced Research Projects Agency) contracts in the United States. The group’s goal is to bring industry and academia leaders together to accelerate vaccine and immunotherapy development. The initial proof of principle work focuses on HIV-1 as its target. However, the consortium could equally apply its intellectual and technical advantage to addressing any other pathogen.

Funding for the program was announced on April 20th. “It’s the way of the future,” Poznansky says. “This is a fascinating opportunity to bring key players together as part of the new wave of research where work that spans from the genome of the pathogen to definitive preclinical testing of a new vaccine in human and animal systems is being done by combining the expertise of all involved.  We each bring our own specialty to the group, but we are integrated right from the beginning. This differs from traditional research where groups worked independently and then if they did hand information over to others – there was a disconnect and it could become quite time consuming, complicated and costly for them to move forward together.  I consider our consortium to be nimble and capable of applying itself to any pathogen at short notice”

This program is fast-moving, Poznansky says, with aggressive timelines to bring their goal to fruition. A prime example of what the group hopes to address is a situation such as the H1N1 flu pandemic in 2009. “We want to be able to respond more quickly to emerging infectious diseases like H1N1, where we saw it take almost two years to create a useful vaccine,” Poznansky says. “Under this type of partnership, it would take months rather than years.”

Poznansky, who hand-picked the consortium members with senior experts from vaccine development advising VIC, credits them with being the best in their respective fields: Evaxion Biotech, which works to identify and develop novel vaccine candidates based on pathogen genomes; biochemist David Baker, PhD, and his team within The Baker Laboratory at the University of Washington in Seattle that designs synthetic proteins that can serve as vaccines; Rhode Island-based immunology company EpiVax, Inc., led by Annie De Groot, MD that uses high-throughput informatics to predicts vaccine components directly from genomic sequences and provides definitive testing of new vaccines in human-like animal models; and ProBioGen, a German-based company specializing in artificial lymph nodes which allow testing of new vaccines in human systems before introduction into patients. Another pivotal person in the consortium’s successful formation was Frances Toneguzzo, PhD executive director of Partners HealthCare Research Ventures and Licensing, and her colleague Rekha Paleyanda PhD, who worked with all parties to create all essential consortium agreements.  The project has been guided in its formation by Dr. Jeff Gelfand, and Tim Brauns, MBA, senior scientific and strategic advisors to VIC.

“We are just in the beginning stages now that the program has been approved,” Poznansky says. “We hope it will represent a new way forward for making better vaccines, faster. It’s exciting to have such a great collaboration.”

For more information on VIC’s projects, visit http://advancingcures.org/.

Providence, RI – April 10, 2012

EpiVax_Tregitope_10April2012

Providence-based biotech EpiVax, Inc. was awarded a new NIH SBIR Phase II grant totaling $1.5M in funding from the National Institutes of Health’s (NIH) NIDDK to explore formulation, dose, route and delivery vehicle for Tregitope through the NIH Small Business Innovation Research (SBIR) program. EpiVax anticipates receiving an additional SBIR award of approximately $775,000 within the next few months, bringing the total to over $2.25 million dollars for the first half of 2012.

The new funding from NIH will allow EpiVax to move this important treatment for autoimmune diseases forward in preclinical studies. Tregitopes were discovered in 2008 by the team of De Groot and Martin at EpiVax and the program is currently managed by Scientific Director and Brown U. Ph.D, Leslie Cousens. The original discovery was published in the journal Blood in 2008.

Tregitopes are linear sequences contained within the framework of monoclonal antibodies and immunoglobulin G (also known as gamma globulin). The Tregitopes act as a natural ‘off switch” and have been shown in standard preclinical models, and by collaborating laboratories, to suppress and treat autoimmune disease, allergy, and to effectively suppress the immunogenicity of co-administered proteins. According to Dr. Srini Kaveri of the Centre de Recherche des Cordeliers (INSERM) in Paris, “It is most likely that some of the well established and successfully practiced therapeutic strategies such as intravenous immunoglobulins to treat several serious autoimmune and inflammatory diseases in order to induce tolerance, may actually be harnessing the potential of Tregitopes”.

Anticipated uses of Tregitope include induction of tolerance to co-administered protein drugs, a market worth more than $100B globally. Also known as biotherapeutics, drugs such as Campath, Rituximab, enzyme replacement therapies such as Myozyme, and blood factors such as FVIII often induce antibodies, rendering the drugs less effective or ineffective. In addition, Tregitopes may have broad applications in Transplant according Nader Najafian, M.D., who is using Tregitopes in research being performed at Harvard Brigham and Women’s Hospital, and therapy for autoimmune diseases such as Multiple Sclerosis. Researcher Samia Khoury M.D., an internationally recognized MS researcher also based at Harvard Brigham and Women’s hospital, says that pre-clinical studies of Tregitope being carried out in her laboratory by researcher Wassim Elyaman, Ph.D., are “promising”. The Tregitope technology won awards from the American Transplant Association (ATA) and from the American Association of Pharmacologists (AAPS) in 2010 and 2011.

The receipt of the original Phase I SBIR grant in 2008 allowed EpiVax to generate substantial evidence that Tregitopes may explain the effectiveness of IVIg, a current leader in auto-immune treatment. In animal models, Tregitope appears to “reset” the immune response away from autoimmunity and towards tolerance, normalizing blood sugar levels.

“This is another great example of the important role the SBIR program has played in helping Rhode Island small businesses,” said Senator Sheldon Whitehouse, who worked to re-authorize the SBIR program in the Senate last year. “I commend EpiVax for its hard work and dedication over the years, and congratulate it on its SBIR grant. This funding will support Rhode Island’s knowledge economy by helping EpiVax continue its important research on the prevention and treatment of harmful diseases.”

The initial target for Tregitope therapy will be Type 1 diabetes (T1D). Each year more than 13,000 young people are diagnosed with T1D. Islet replacement therapy is still in the experimental stage for individuals with advanced disease, but EpiVax believes that T1D-Tregitope therapy will facilitate this novel treatment for individuals in the later stages of T1D. Furthermore, preliminary studies carried out by EpiVax and collaborators indicate that Tregitope may be useful for inducing tolerance to transplants, protein drugs, and blood replacement therapies, suggesting that Tregitope may be useful for patients with other auto-immune diseases. EpiVax will use this new round of funding to develop a dosing and delivery procedure for Tregitope therapy in preparation for an IND application. Preliminary “Safety and Toxicity” studies are also supported by the NIH Phase II.

“Developing more specific therapies to promote tolerance to the beta cell antigens that trigger the autoimmune response is a critical component of a comprehensive therapeutic approach to type 1 diabetes,” said Julia Greenstein, Ph.D., assistant vice president of cure therapies for JDRF, whose previous funding for EpiVax helped the company derive preliminary data to support the new NIH funding. “It’s great to see the NIH support EpiVax’s approach as this therapy may have the potential to reduce the harmful immune responses to the insulin-producing beta cells, thereby preserving the body’s ability to make its own insulin.”

“The endorsement, and more so the continued funding, by the National Institutes of Health of EpiVax’s Tregitope program, is further validation of the promising research pioneered by Dr. De Groot and her colleagues and collaborators,” stated Richard G. Horan, managing director at the Slater Technology Fund. “Rhode Islanders have been well-served by the support provided EpiVax from the Slater Fund in the company’s early years. In addition to generating a return on the fund’s investment, the company has generated over a decade of high value, high wage jobs funded by steadily-increasing grants and contracts with pharmaceutical and biotech companies. It’s a great example of academic innovation translating into robust economic development in biotechnology.”

Note- More information about current research on Tregitope will be available to the public at EpiVax’s 4th Annual Tregitope Symposium will be in Baltimore following IIR’s 13th Annual Immunogenicity for Biotherapeutics. Seating is limited. Please contact us for the hotel discount code and to reserve a seat.

For further information and to register for our seminar, please contact CMillerIV[at]EpiVax.com or AnnieD[at]EpiVax.com.

For more information on Tregitopes, the original paper can be found at this link:
http://tinyurl.com/ASDeGroot-Blood-2008.

An animation describing the proposed mechanism of action can be found at:http://www.epivax.com/epivax-animation4.html

For more information about Professor Anne S. De Groot, M.D.
see http://www.immunome.org.

For the relevance of Tregitope to biologics
http://tinyurl.com/ASDeGroot-Clin-Immunol-2009.

Tregitopes were discovered in 2008 by the team of De Groot and Martin at EpiVax; the original discovery was published in the journal Blood in 2008 [direct link to reference here]. These are linear sequences contained within the framework of monoclonal antibodies and immunoglobulin G (also known as gamma globulin). The Tregitopes act as a natural ‘off switch” and have been shown in standard preclinical models, and by collaborating laboratories, to suppress and treat autoimmune disease, allergy, and to effectively suppress the immunogenicity of co-administered proteins.

According to Dr. Kaveri, “It is most likely that some of the well established and successfully practiced therapeutic strategies such as intravenous immunoglobulins to treat several serious autoimmune and inflammatory diseases in order to induce tolerance,  may actually be harnessing the potential of Tregitopes”.

Anticipated uses of Tregitope include induction of tolerance to co-administered protein drugs, a market worth more than $100B globally. Also known as biotherapeutics, drugs such as Campath, Rituximab, enzyme replacement therapies such as Myozyme, and blood factors such as FVIII often induce antibodies, rendering the drugs less effective or ineffective. The presence of Tregitopes in monoclonals is directly related to lower immunogenicity in clinical use, a finding that was previously described and published by De Groot and Martin.

In addition, Tregitopes may have broad applications in Transplant according Nader Najafian, M.D., who is using Tregitopes in research being performed at Harvard Brigham and Women’s Hospital, and therapy for autoimmune diseases such as Multiple Sclerosis. Researcher Samia Khoury M.D., an internationally recognized MS researcher also based at Harvard Brigham and Women’s hospital, says that pre-clinical studies of Tregitope being carried out in her laboratory by researcher Wassim Elyaman, Ph.D., are “promising”. The Tregitope technology won awards from the American Transplant Association (ATA) and from the American Association of Pharmacologists (AAPS) in 2010 and 2011.

UNIVERSITY OF RHODE ISLAND
PROVIDENCE, RHODE ISLAND
OCTOBER 15-17, 2012

The Institute for Immunology and Informatics (iCubed) is pleased to announce the 6th Annual Vaccine Renaissance Conference scheduled for October 15-17, 2012 in Providence, Rhode Island.

We are again developing an interactive program with ample time for the exchange of ideas among experts in vaccine research, delivery, clinical trials and basic immunology. Nationally recognized academic, pharmaceutical, National Institutes of Health, and United States Department of Agriculture researchers will attend.

Through this year’s list of noted speakers as well as our diverse agenda, we plan to focus on vaccines for neglected tropical diseases, cancer, biodefense, as well as vaccines for animals.

Please visit Immunome.org for further updates regarding registration, poster abstract submission details, and the conference agenda.

We hope to see you all in Providence this October!

April 2012

Identifying Host Cell Genome Epitopes and What They Mean for Immunogenicity (invited talk – Annie De Groot and Lenny Moise)

4^th Annual Tregitope Update: Baltimore (Following IIR Event)

Contact Curtis at CMillerIV@EpiVax.com to reserve a seat.

Tregitope Applications to Tolerance Induction in Autoimmune Diseases, Saturday, May 5, 10:15-12:15AM in the Hynes Convention Center Room 312. Oral and Poster #: P1565; Abstract #1337905

Tregitope Mechanism of Action and Applications for Tolerance Induction; Oral Presentation: Saturday, May 5, 10:15-12:15AM in the Hynes Convention Center Room 312. Poster #: P1569; Abstract #: 1337698

Regulating Immune Responses to Biologics: Epitope Prediction and Modulation. Poster #: P1153; Abstract #: 1338450

Invited Plenary IV: Tregitope: Applications to Tolerance induction in Autoimmune Disease. (De Groot, Cousens, et al.)

Tregitope mechanism of Action and Mechanism for Tolerance Induction. Abstract ID: 816 Oral Session. (De Groot, Cousens, et al.)

IgG-derived T cell epitopes (Tregitopes) suppress immune responses by activating nTregs.  (Yan Su, David Scott, others) Abstract ID: 852 Oral Session.

Tregitope suppression of anti-DNA mimotope immune responses. Scott et al.  Abstract ID: 853 Oral.

Tregitopes enhance regulatory T cell expansion and attenuate the autoimmune responses in a murine model of multiple sclerosis. Elyaman Khoury, et al.  Abstract ID: 748 Poster.

Adjuvant effects of C3d are mediated through the activation of C3d-specific autoreactive T cells. Messitt, De Groot, Knopf, et al. Abstract ID: 764 Oral.

Regulating Immune Responses to Biologics: Epitope Prediction and Applications. Poster #: M1035

Tregitope Applications to Tolerance Induction in Autoimmune Diseases. Poster #: W3002

Tregitope Mechanism of Action and Applications for Tolerance Induction. Poster #: W3001

Also in San Diego May 2012: Digestive Diseases Week May 19-22, 2012

 June 2012

 Bio 2012 – Interactive Session – Panel on Immunogenicity

“Cutting Edge”: Making Better Biologics by Harnessing Tolerance and Immunogenicity”

Here in Tokyo, where we just participated in the “Westin Immunogenicity Seminar”, we are finding impressive resilience and focus on the future. The twin disasters of tsunami and earthquake appear to be in the past, and signs that say “Japan, rising again” greet travelers, as do signs saying “Thank you”, to the countries and corporations who contributed to the recovery from the events of March 2010. Resilience and focus are virtues worth emulating, whether in life or in biotech.

Another virtue worth emulating in life and biotechnology is honesty. That should be the backbone of every relationship, whether corporate or human. We definitely prize honesty at EpiVax, and it is for that reason that we share our work in public, non-commercial forums and submit our research for publication.

For example, we know that Host Cell Proteins (HCP) are a new focus for the FDA. So we’re working on analyzing the published CHO genome using methods published previously in our vaccine design papers.* Which are the most immunogenic epitopes in CHO? Well, they’ll be (i) upregulated in culture, (ii) secreted, and (iii) different from human in key regions of the CHO protein sequence that can be presented to T cells by human HLA. See here for the application of this theory to biologics. See here for my previous post on the CHO genome and come to IIR if you want to hear more.

As we’ve published, not all T cell epitopes are bad, in fact, some are good. We call those Tregitopes. We will also be presenting data on Tregitope during a plenary at the Autoimmunity conference in Granada, and at the AAI meeting in Boston in May. You can also find a list of our recent papers here and our scheduled presentations here.

And finally, the 4th Annual Tregitope Symposium will be held on April 20th, 2012 at the same location as IIR’s 13th Annual Immunogenicity for Biotherapeutics. There’s a small fee for attending that covers the cost of lunch. Please contact us to reserve a seat.

We look forward to open and honest discussions with our scientific colleagues!

And thanks for reading this post.

Sincerely, Annie

*A comprehensive review defining the steps we use to identify regions of proteins that are immunogenic, published in Immunology and Cellular Biology (a Nature journal) can be found here.

Sponsored by the University of Rhode Island Institute for Immunology and Informatics and EpiVax, Inc.

Register by email to: Curtis Miller at CMillerIV@EpiVax.com

Westin Immunogenicity Seminar 2012: Friday March 16th 2012

The Westin Tokyo, 1-4-1 Mita Meguro-ku, Tokyo 153-8580 Japan

Speakers:

Shingo Niimi, Ph.D., Immunogenicity Expert from NIHS

Annie De Groot M.D. Director and Professor, Institute of Immunology and Informatics,University of Rhode Island and CEO/CSO EpiVax;

Tim Messitt, Ph.D. Expert on Immunogenicity Assays, EpiVax, Inc.

Frances Terry Immunoinformatics / Bioinformatics Specialist, EpiVax, Inc.

Keizo Yoshida Ph.D., EpiVax Asia

Note- In addition to the Westin Seminar, we are offering a Hands-On Demonstration of the iVAX Web-based tool for Vaccine Design at a location near the University of Tokyo Medical Sciences Campus on Monday the 19th of March 2012. iVAX is available for use Free of Charge for research on Neglected Tropical Diseases from the Institute of Immunology and Informatics, URI. Please contact us if you are interested in this additional free vaccine design seminar.

To register for either seminar, contact CMillerIV@EpiVax.com or YoshidaKeizo@gmail.com

For more information on Tregitopes, please see this link: http://tinyurl.com/EpiVax-AAPS-Award. The original paper can be found at this link: http://tinyurl.com/ASDeGroot-Blood-2008. For more information about Professor Anne S. De Groot, M.D. see http://www.immunome.org/.
For the relevance of Tregitope to protein medicine: http://tinyurl.com/ASDeGroot-Clin-Immunol-2009.

They describe how EpiMatrix works, and go on to say, that “the EpiMatrix platform is also closely tied with additional computational tools such as ClustiMer (scans EpiMatrix results for T-cell epitope ‘clusters’), BlastiMer (automated BLAST search tool), OptiMatrix (involved in deimmunizing sequences), Conservatrix (involved in finding conserved epitopes) and Vaccine CAD (an in silico vaccine design algorithm).”

The authors, Danylo Sirskyj, Francisco Diaz-Mitoma, Ashkan Golshani, Ashok Kumar and Ali Azi of University of Ottawa, also state that  “One of the more comprehensive programs seems to be EpiMatrix from EpiVax Inc. (http://www.epivax.com/).”

We couldn’t agree more. We like balmy weather, and really good chocolate too. What’s not to like?

I am always thrilled to meet people who are challenging paradigms. At a meeting last week, I heard about using ADCC (antibody dependent cytotoxicity) to kill tumors, and learned that clinicians are now using a cocktail of monoclonals, depending on the patient’s cancer gene profile. We’re only a step away . . . from using the same cancer profile to generate personalized cancer vaccines. I can see the future!

What’s this all about? Well, some clinicians are using a multi- Mab-cocktail approach to treating cancer (remember HIV and TB? yes, just like that). Louis Wiener, from Lombardi Cancer Center at Georgetown, was the speaker. He has used gene upregulation to identify cancer targets for his patients, and then combines antibodies in a cocktail in a personalized medicine approach. He explained that Mab targeting creates an opportunity to use ADCC to destroy tumors, leading to presentation of antigens to T cells. Now that makes more sense to me than postulating that the antibodies (Herceptin, e.g.) are clearing the cancers! (I admit to a bit of a T cell bias).

I always feel better if I stretch my brain a bit, how about you? If you are interested in stretching your brain a bit with us, check out our talk schedule and come put your mind (and hands) to work at one of our workshops. See here for the schedule. I look forward to seeing you!