hpv58 type e6/e7 fusion gene and therapeutic compound gene vaccine

A technology of fusion gene and gene vaccine, applied in gene therapy, drug combination, microorganism-based methods, etc., can solve the problems of ignoring antigenicity, ineffective cervical tissue treatment, virus escape, etc. Tumor function, the effect of enhancing immune recognition

Inactive Publication Date: 2011-12-14
广西医科大学附属肿瘤医院
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  • Abstract
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  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, this type of vaccine has the following problems: since the L1 and L2 capsid proteins are not expressed in cervical cancer and precancerous lesion tissues, the above-mentioned vaccines can only be used to prevent HPV58 infection, but for cervical tissue that has already been infected or pathological changes Ineffective treatment
This type of vaccine has the following problems: Although E1 and E2 proteins are involved in the replication of virus episomes and the transcription of early viral genes, they may be good target antigens in the early stage of infection, but the expression levels of E1 and E2 proteins are very low so that they are difficult to be detected by the immune system. recognized, allowing the virus to escape
However, this type of vaccine has the following problems: because only the HPV58E7 gene is used as an antigen and the antigenicity of another important gene E6 is ignored, and there is no synergistic related adjuvant to break immune tolerance, so the effect of the vaccine needs to be improved
(2) No use of E6 and E7 fusion genes as target antigens
[0007] There are no related reports on the development of chimeric vaccines using HPV58L1 and L2 combined with E6 and E7 as target antigens

Method used

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  • hpv58 type e6/e7 fusion gene and therapeutic compound gene vaccine
  • hpv58 type e6/e7 fusion gene and therapeutic compound gene vaccine
  • hpv58 type e6/e7 fusion gene and therapeutic compound gene vaccine

Examples

Experimental program
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Embodiment Construction

[0031] Study on the Safety and Effectiveness of HPV58 Vaccine

[0032] One, PVAX1-HPV58mE6E7Fc-hIL12 vaccine construction (such as Image 6 )

[0033] The two keys of immunotherapy are suitable antigen and efficient carrier. In terms of antigen selection, since the early genes E6 and E7 of HPV are necessary to maintain its malignant phenotype, they are expressed in all stages of tumor development from the beginning of virus infection to the advanced stage of cancer, which can induce the body to produce and maintain strong The specific CTL with viral antigen as the target molecule is still the target antigen commonly selected for the development of HPV therapeutic vaccines so far. When designing the antigen, the inventor first removed the termination codes of the HPV58 E6 and E7 genes, and fused the E6 and E7 genes into the HPV58E6E7 fusion gene. Since HPV E6 and E7 are oncoproteins, viral DNA may integrate into the host cell genome, induce malignant transformation of cells,...

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Abstract

The invention discloses an HPV58 type E6 / E7 fusion gene. The fusion gene removes the termination codes of the HPV58 type E6 and E7 genes, and at the same time combines the 50th, 63rd and 106th amino acids on the E6 protein with the 24th amino acid on the E7 protein. , 26 and 92 amino acids are all mutated to glycine. The invention also discloses a therapeutic composite gene vaccine prepared by using the fusion gene, which uses the fusion gene as a target antigen and human interleukin 12 (hIL12) as an antigen adjuvant. The fusion gene and therapeutic compound gene vaccine provided by the present invention have high safety, strong immune effect and ideal antitumor, and provide a better choice for the treatment of cervical cancer and precancerous lesions related to HPV58 infection, especially suitable for HPV58 high Infected Chinese and Asian cervical cancer patients.

Description

technical field [0001] The invention relates to the field of prevention and treatment of cervical cancer, in particular to human papillomavirus type 58 (hereinafter referred to as HPV58) E6 / E7 fusion gene and therapeutic compound gene vaccine. Background technique [0002] Cervical cancer is one of the common gynecological malignancies, and its incidence rate ranks second among female malignancies, second only to breast cancer. There are about 131,500 new cases of cervical cancer in my country every year, accounting for 28.8% of the total number of new cases of cervical cancer in the world, and about 50,000 patients die of cervical cancer every year, most of which are located in economically underdeveloped western regions such as Guangxi. At present, traditional methods such as surgery, radiotherapy, and chemotherapy are not effective for patients with advanced cervical cancer, and the 5-year survival rate is only 50%. Etiological studies of cervical cancer have shown that:...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C12N15/62A61K48/00A61K39/12A61P35/00C12N15/85C12R1/93
Inventor 王鹤于继云李力
Owner 广西医科大学附属肿瘤医院
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