(WO/2010/027973) HUMAN PAPILLOMAVIRUS / LI-KEY HYBRIDS AND METHODS OF USE
Applicants: ANTIGEN EXPRESS, INC. [US/US]; Biotech Three, 4th Floor One Innovation Drive Worcester, MA 01605 (US) (All Except US).
XU, Minzhen [CN/US]; (US) (US Only).
HOFE, Eric, Von [US/US]; (US) (US Only).
Inventors: XU, Minzhen; (US).
HOFE, Eric, Von; (US).
Every year, 470,000 cases of cervical cancer are diagnosed. Essentially 100% of cervical cancers contain HPV of the high-risk type (HPV 16 or 18), persistent infection of the cervix with these viruses is considered to be the necessary cause of the disease (90% of other ano-genital cancers also contain HPV). Oral cancer, penile cancer and some neck cancer might be related to HPV infection as well. There are no good therapies when metastasis of HPV induced cancers such as cervical cancer occurs and thus effective new therapies are needed urgently.
Gardasil, a virus like particle that targets the L1 protein of HPV types 6, 1 1 , 16 and 18 protects women from infection by HPV close to 100%. This type of vaccine mainly induces a humeral immune response generating antibodies that can neutralize the virus. Gardasil is thus an effective vaccine for preventing HPV infection. However, this kind of vaccine is ineffective for treating HPV+ cancers since both CD4+ and CD8+ T cell immunity must be induced in order to eradicate the HPV+ cancers.
Accumulating data indicate that immunotherapy for cervical cancer and other HPV+ cancers holds promise. The expression of the HPV E6 and E7 genes is found in most cervical cancers as well as other HPV+ cancers, indicating that the HPV oncogenic proteins, E6 and E7, are critical for the induction and maintenance of cellular transformation. The specific expression of these genes in the majority of the HPV+ carcinomas suggests that they are good targets for immunotherapy.
Presented herein, are embodiments of the present invention including a novel and non-obvious method that significantly enhances the efficiency of HPV peptide vaccine. In this regard, the present invention is directed towards compositions comprising li-key/HPV hybrid peptides and nucleotide sequences encoding said peptides. The present invention is also directed towards methods of prevention of HPV infection by administration of one or more compounds of the present invention to a subject. Further, the present invention is directed towards the treatment of diseases in which HPV infection is at least part of the etiology of the disease. Such diseases include, but are not limited to, warts and precancerous or cancerous lesions such as cervical cancer, penile cancer and certain neck cancers. In another aspect of the present invention, it is contemplated that the HPV sequences of the present invention are useful for the inoculation and vaccination of subjects for the treatment or prevention of diseases in which HPV infection is at least part of the etiology of the disease.
In another aspect, the present invention relates to a method to improve the potency of DNA and peptide vaccines containing MHC Class ll-presented epitopes of HPV antigens of interest. The present invention involves priming the immune system of a subject with li-Key hybrid peptides such that the potency of a subsequently administered DNA or peptide vaccine is augmented. The li-Key construct may be administered in the form of a nucleic acid construct encoding the li-Key hybrid peptide.
See WIPO details here.
This Is Generex Biotechnology Pipeline Review
Antigen Express
Antigen Express is the fully owned life science subsidiary of Generex Biotechnology. Antigen Express is a platform and product-based company developing proprietary vaccine formulations for large, unmet medical needs. Their focus is on stimulating critical members of the immune response, known as T helper cells. The technology allows for antigen-specific stimulation or suppression of a T-helper response to virtually any antigen of known pathogenic potential. Antigen Express is building a deep pipeline of therapeutics aimed at a variety of major diseases, including cancer, infectious diseases and autoimmune-based syndromes.
Early efficacy analysis of the AE37 vaccine in a Phase II study
Click the logo to see the results for AE37 that were presented at the 2012 ASCO Breast Cancer Symposium
Peptide Vaccine Stimulates Immune Response in Patients With Breast Cancer
Click the logo to read about the results for AE37 that were presented at AACR 2012
Antigen Express President Dr Eric von Hofe
The President of Antigen Express is Dr Eric von Hofe, who has been impressive with advancing Antigen Express' pipeline and entering into smart collaborations. Dr. von Hofe joined Antigen Express in November of 2003. Prior to this time he held two positions at Millennium Pharmaceuticals; first as Program Director for Target Validation, where he presided over technology development efforts for Aventis and Cereon, and second as Director of Programs and Operations, Discovery Research. He received his Ph.D. from the University of Southern California and was a postdoctoral fellow at the University Hospital of Zurich and Harvard. From 1989 to 1992 he was Assistant Professor of Pharmacology at the University of Massachusetts Medical School. Click on the image of Dr von Hofe to read the abstract for his latest peer review article regarding cancer vaccines.
The AE37 Ii-Key synthetic peptide vaccine
Click on image to enlarge. Harvard scientists, who founded and lead Antigen Express, have pioneered and patented technology that modify MHC class II epitope peptides with a fragment of the MHC class II-associated invariant chain. Antigen Express recently reported interim results from a Phase II trial of the AE37 HER2/neu Ii-Key modified peptide vaccine for patients treated for breast cancer who are at high risk of relapse. While there was a 7% relapse rate in the control arm, there were no relapses in the Ii-Key peptide arm (AE37) when analyzed at the 13-month time point. A review article co-authored by Dr. Eric von Hofe, Ph.D., President of Antigen Express, entitled "A New Era in Anticancer Peptide Vaccines", will appear in an early 2010 edition of the journal Cancer, the International Interdisciplinary Journal published by the American Cancer Society. An advantage of using the type of active immunotherapy offered by AE37, as opposed to passive immunotherapy such as treatment with Herceptin, is that activated immune cells can detect and destroy cancer cells expressing much lower levels of HER-2/neu than is needed for recognition by Herceptin.
San Antonio Breast Cancer Symposium December 2009
Positive AE37 Phase II Interim results were reported at the San Antonio Breast Cancer Symposium in December 2009. Click the SABCS logo to view the poster presentation for AE37's Interim Phase II results, while the abstract text will be provided below.
Antigen Express' Ii-Key Peptide Vaccine Platform Technology
Click on the image for Antigen Express' pipeline to enlarge. AE37 is a novel peptide vaccine that is the product of a proprietary technology platform established at Antigen Express designed to increase the antigen-specific stimulation of CD4+ T helper cells. AE37 is capable of eliciting HER2/neu-specific immune responses, even without the use of an adjuvant. AE37 is the first peptide-based cancer vaccine to show potency in the absence of an immunoadjuvant.
Mary Crowely Cancer Research Center is Fully Funding the AE37 Combo Vaccine Study
Click on the Mary Crowley logo, provided above, to see the clinical trial listing for the AE37 Combo Vaccine
About Me
- Rich Steffens
- Rich Steffens has grown up in New Jersey, is a successful businessman, and studies social media trends amongst life science and biotech companies. His family is deeply influenced by the ill effects of diabetes. I am not qualified to offer investment or medical advice, and make no claims that I am an expert in these areas. I seek to share and learn.
The Future of Insulin Treatment
Dr Gerald Bernstein, Generex VP and former Pres of the ADA, was featured in an online video at the Doctor's Channel in a segment titled "Diabetes & Endocrinology Oral Insulin Delivery with Oral-Lyn". With many new insulin based drugs on the horizon, Dr Bernstein explains both the history of insulin treatment and what he believes to be the best future option- Oral-lyn. Click on the image of the current new insulin based drugs in development to view the video.
Oral-lyn's time profile; insulin only when a diabetic needs it, bringing less risk of hypoglycemia
This image, which you can click to enlarge, illustrates that with its very fast onset and offset of action, Oral-lyn buccal insulin spray may offer less risk of postprandial hypoglycemia as compared to conventional injected insulin therapy. Hypoglycemia is a life-threatening risk, and along with injections is the most important obstacle towards achieving good metabolic control. With each spray of the RapidMist device one unit of meal time Oral-lyn buccal insulin is said to be rapidly delivered into the bloodstream. The amount of sprays given is determined by the amount of insulin each unique diabetic requires to cover a meal. The company informs that the insulin only remains in the bloodstream during the time period the diabetic needs it, promising a safer and simpler approach.
The extended action of injectables may lead to hypoglycemia; the insulin often lingers too long
In this graph, which you can click to enlarge, we can see the long tail of both meal time analogues and regular insulin. Analogue prandial insulin is dosed approx 15 minutes before a meal, peaks in an hour, and with a duration of effect of 4 hours. Regular insulin is dosed 30 minutes before a meal, peaks in 2 hours and lingers up to 6 hours in the bloodstream. This slow acting tail activity often causes low blood sugar levels to occur after the glucose spike provided by the meal starts to decline. Generex states that Oral-lyn is taken right before the first bite of the meal, immediately begins to be absorbed in the inner lining of the mouth, peaks in 30 minutes, and blood sugar levels cleanly return to baseline within two hours. Generex finds there is no tail of activity with Oral-lyn as there is with all other forms of injectable insulin, so they believe the risk of postprandial hypoglycemia is greatly minimized. If blood levels are back at baseline after the meal, there is no reason to gorge on post meal snacks to offset any lingering insulin, which helps avoid unhealthy weight gain. The unique time action profile for Oral-lyn, if proven in the Phase III study, may provide greater flexibility in usage, as well as the ability to take small dose sprays before a snack when that tasty treat simply can not be resisted. Another main advantage for Oral-lyn may be its ability to mimic the first-phase insulin response seen in a healthy person. This first-phase insulin release is one of the first functions that people with diabetes lose. In healthy people our bodies release insulin within 10 minutes after eating.
Oral-lyn Buccal Insulin X-RAY imagery proves no deposition into the lungs
Unlike Mannkind's Afrezza, in which a powder insulin formulation is inhaled into and absorbed by the lungs, Oral-lyn is delivered as a fine spray to the buccal cavity by the RapidMist delivery system. Generex states the result is rapid insulin absorption through the buccal mucosal lining of the mouth without pulmonary (lung) exposure. The lungs, like all other vital organs in the body, are already a target of diabetes leading to lower lung function over time. The lungs are meant to process gasses, and not proteins. I think that Generex, via Oral-lyn buccal insulin, avoids potential pulmonary complications in a simpler and safer approach. Click on the provided X-Ray image to learn more.
Prandial insulin dosing is now as simple as a spray
Oral-lyn is available in a US FDA approved Treatment IND as well as in Phase III trials as a 1 UNIT per spray dose. For Oral-lyn, the delivery devise appears built to provide fine tuning post meal dosing. It appears as simple as taking another quick spray. In my opinion, as the safety concerns swirl around prospects for inhalable insulin, the Oral-lyn buccal insulin Treatment IND sounds like a great marketing advantage, since more and more diabetics and physicians will learn of buccal insulin as Generex works towards full approval.
Generex Oral-lyn Buccal Insulin
"Patients who are needle averse face a serious barrier to their recommended treatment," warns Generex "Generex Oral-lyn promises a pain-free alternative to injectable insulin, which is good news especially for older patients and children who find needles uncomfortable." Click on the image provided above to learn more about aversion to injections and diabetes.
Dr Gerald Bernstein, VP Medical Affairs Generex, former President of American Diabetes Association
Click on the photo of Dr Bernstein to view his interview on FOX Health. Dr Bernstein recently commented further on the unique safety profile for Oral-lyn: "It’s extremely safe by all the studies that have been done so far, including two years in animal tests. We haven’t seen allergic reaction. The lining of the mouth hasn’t shown any abnormalities. The buccal mucosa is an extra-tough and resilient tissue, it’s beaten up all the time. People bite themselves or burn themselves. Whatever doesn’t get absorbed is going to go to the stomach. Now the insulin molecule is unprotected and therefore it will be denatured by the acid and then broken down. There are no side effects." Dr Bernstein is an attending physician at Beth Israel Medical Center, and physician emeritus at Lenox Hill Hospital and Montefiore Medical Center, all in New York. He was formerly Director of the Beth Israel Health Care Systems Diabetes Management Program. Dr. Bernstein was president of the American Diabetes Association in 1998-99 and was for many years a member of the ADA's Board of Directors and its Executive Committee. He received the ADA's Banting Medal for Service in 1999. Dr. Bernstein presently serves on several ADA committees and on the Board of Directors of the American Diabetes Association Research Foundation.
Buccal Absorbtion
RapidMist Buccal Drug Delivery Device
