(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.
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