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Modified orthopoxvirus vectors

A technology of vaccinia virus and vaccinia, which is applied in the field of immunotherapy for cell proliferation diseases, and can solve problems such as small clinical effects

Pending Publication Date: 2021-11-16
OTTAWA HOSPITAL RES INST +1
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0007] Although the use of orthopoxviruses as clinical oncolytic vectors is a promising paradigm for cancer therapy, recent clinical candidates have shown only modest clinical gains due to toxicities such as pox lesions in patients and immunosuppressive side effects

Method used

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  • Modified orthopoxvirus vectors
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  • Modified orthopoxvirus vectors

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Experimental program
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Effect test

Embodiment approach 191

[1859] 197. A method of treating cancer in a mammalian patient, said method comprising administering to the mammalian patient a therapeutically effective amount of the pharmaceutical composition according to embodiment 191.

[1860] 198. The method according to embodiment 196 or 197, wherein the mammalian patient is a human patient.

[1861] 199. The method according to any one of embodiments 196 to 198, wherein the cancer is selected from the group consisting of leukemia, lymphoma, liver cancer, bone cancer, lung cancer, brain cancer, bladder cancer, gastrointestinal cancer, breast cancer, cardia Cancer of the cervix, uterus, head and neck, gallbladder, larynx, lip and oral cavity, eye, melanoma, pancreas, prostate, colorectum, testis and throat.

[1862] 200. The method of embodiment 199, wherein the method further comprises administering an anti-PD1 antibody or an anti-PD-L1 antibody to the mammalian patient.

[1863] 5.7.5. Group 5

[1864] 1. A nucleic acid comprising a...

Embodiment 6-78

[2824] 6.6. Syncytia in Example 6-786-O cells

[2825] Monolayers of 786-O cells were infected with Copenhagen wild-type or CopMD5p3p virus. After 24 h, images were acquired with EVOS at 10× magnification (see Figure 10 ). This is additional evidence that syncytia occurs. exist Figure 9 In , the expression patterns of the plaques are shown. In the current experiment, monolayers of cells were infected without covering. Most of the cells infected by CopMD5p3p virus were confluent.

[2826] 6.7. Example 7 - Tumor Control and Weight Loss in a Mouse Model

[2827] Nude CD-1 mice were inoculated with HT-29 human colon carcinoma xenografts. Once a subcutaneous tumor of approximately 5 mm × 5 mm in size has formed, use 1 × 10 7 Mice were treated intravenously with PFU of either vaccinia virus three times at 24 h intervals (dashed line). Tumor size and weight loss of the mice were measured approximately every other day (see Figure 11 ). This experiment showed that CopMD5p...

Embodiment 10

[2834] 6.10. Example 10 - Immunogenicity of vaccinia in human PBMC

[2835] PBMCs were isolated from the blood of healthy human donors (n=2). PBMC were incubated with either vaccinia for 24 h and early activation markers were examined using flow cytometry (see Figure 15 ). This experiment shows that CopMD5p3p is more immunogenic and can be more easily detected by immune cells. This is considered a desirable trait because OV replication in tumor tissue requires the activation of immune cells for a successful anti-tumor immune response.

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Abstract

The disclosure relates to modified orthopoxvirus vectors, as well as methods of using the same for the treatment of various cancers. The disclosure provides modified orthopoxvirus vectors that exhibit various beneficial therapeutic activities, including enhanced oncolytic activity, spread of infection, immune evasion, tumor persistence, capacity for incorporation of exogenous DNA sequences, amenability for large scale manufacturing, and safety.

Description

[0001] Cross References to Related Applications [0002] This application claims U.S. Provisional Patent Application No. 62 / 930,524, filed November 4, 2019, U.S. Provisional Patent Application No. 62 / 872,699, filed July 10, 2019, and U.S. Provisional Patent Application No. 62 / 872,699, filed December 21, 2018 62 / 784,372, the disclosures of which are hereby incorporated by reference in their entirety. [0003] sequence listing [0004] This application is incorporated by reference and has a Sequence Listing filed with this application in the form of an ASCII text file named 14596-051-228_SL.txt, created on December 18, 2019 and having 1,252,729 bytes of size. 1. Technical field [0005] The invention relates to the field of immunotherapy, eg for the treatment of cell proliferative disorders such as cancer. Specifically, the present invention relates to genetically modified orthopoxviruses and methods for their preparation and use. 2. Background technology [0006] The immu...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C12N15/863A61K35/768A61P35/00C07K14/07C07K14/54C07K14/575C07K16/28C12N15/12C12N15/13C12N15/24C12N15/39C12N5/10C12N7/01
CPCA61K35/768A61P35/00A61K39/3955C07K16/2818A61K2039/505C07K14/5434C07K14/52C12N7/00C12N2710/24121C12N2710/24122C12N2710/24132C12N15/86C12N2710/24143A61K2300/00A61K38/00
Inventor 约翰·C·贝尔迈克尔·S·许马修·Y·唐阿德里安·佩林卡罗琳·J·布雷特巴切迈克尔·F·伯吉斯史蒂文·H·伯恩斯坦
Owner OTTAWA HOSPITAL RES INST