Replication-deficient arenavirus particles and tri-segmented arenavirus particles as cancer vaccines

An arenavirus, defective technology, applied in the direction of viruses, viruses/phages, virus antigen components, etc., can solve the problems of chemotherapy side effects and other problems

Pending Publication Date: 2019-08-23
HOOKIPA BIOTECH GMBH
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, chemotherapy is also known to have serious side effects and is not always effective

Method used

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  • Replication-deficient arenavirus particles and tri-segmented arenavirus particles as cancer vaccines
  • Replication-deficient arenavirus particles and tri-segmented arenavirus particles as cancer vaccines
  • Replication-deficient arenavirus particles and tri-segmented arenavirus particles as cancer vaccines

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0630] 8.1 Example 1: The effect between r3LCMV treatment and chemotherapy

[0631] The potential synergy between r3LCMV treatment and low-dose chemotherapy (cyclophosphamide treatment) was evaluated in the B16F10 mouse melanoma model.

[0632] On day 0, place 1×10 5 B16F10 tumor cells were subcutaneously implanted into C57BL / 6 mice. Subsequently, mice were kept untreated (group 1), treated intraperitoneally with 2 mg cyclophosphamide on day 6 (group 2), and injected intravenously with 2.1 × 10 5 PFU (total) of carrier mix (7 × 10 4 PFU of r3LCMV-GP100, r3LCMV-Trp1 and r3LCMV-Trp2) (group 3), or combined treatment with cyclophosphamide (day 6) and r3LCMV-vehicle mixture (day 7) (group 4). The genome organization of the r3LCMV construct is basically as follows figure 2 For r3LCMV-GFP art As shown, except that the construct has an ORF encoding the antigens of interest, namely GP100, Trp1 and Trp2, instead of the GFP ORF. Tumor growth (Fig. 3A) and survival of animals foll...

Embodiment 2

[0634] 8.2 Example 2: The effect between r3LCMV treatment and chemotherapy in the HCmel3 model

[0635] The potential synergy between r3LCMV treatment and low-dose chemotherapy (cyclophosphamide treatment) was evaluated in the HCmel3 mouse melanoma model. HCmel3 tumor cells are derived from primary Hgf-Cdk4 R24C melanoma.

[0636] On day 0, HCmel3 tumor cells (4×10 5 cells) were subcutaneously implanted into C57BL / 6 mice. Mice in groups 3 and 4 were treated with 2 mg cyclophosphamide (CTX) ip when all tumors were palpable. On day 16, use 7×10 4 Mice in groups 2 and 3 were injected intravenously with RCV FFUr3LCMV-Trp2. Use 1×10 5 Mice in group 4 were immunized intravenously with RCV FFU r3PICV-Trp2.

[0637] The genome organization of the r3LCMV construct is basically as follows figure 2 For r3LCMV-GFP art As shown, except that the construct has an ORF encoding the antigen of interest, Trp2, instead of the GFP ORF. Tumor growth following tumor challenge was monitore...

Embodiment 3

[0639] 8.3 Example 3: HgfxCDK4 R24C / R24C Effects between r3LCMV treatment and chemotherapy in mice

[0640] HgfxCDK4 R24C / R24CThe model is a syngeneic model in which mice develop spontaneous tumors showing some similarities to human melanomas (Landsberg et al., Autochthonous primary and metastatic melanomasin Hgf-Cdk4 R24C mice evade T-cell-mediated immune surveillance. 2010; Bald et al., Immune cell-Poor Melanomas benefit from PD-1 Blockade after targeted typeI IFN activation, 2014).

[0641] in HgfxCDK4 R24C / R24C The potential synergy between r3LCMV treatment and low-dose chemotherapy (cyclophosphamide treatment) was evaluated in a mouse model. Mice remained untreated (group 1) and were treated with 2 mg cyclophosphamide ip when tumors were palpable (approximately day 60) (group 2), and when tumors were palpable (approximately day 60) were treated with The vehicle mixture (r3LCMV-GP100, r3LCMV-Trp1 and r3LCMV-Trp2) was injected intravenously (group 3) or treated with a c...

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Abstract

The present application relates generally to genetically modified arenaviruses that are suitable vaccines against neoplastic diseases, such as cancer. The arenaviruses described herein may be suitableas vaccines and / or for treatment of neoplastic diseases and / or for the use in immunotherapies. In particular, provided herein are methods and compositions for treating a neoplastic disease by administering a genetically modified arenavirus in combination with a chemotherapeutic agent, wherein the arenavirus has been engineered to include a nucleotide sequence encoding a tumor antigen, tumor associated antigen or antigenic fragment thereof.

Description

[0001] This application of the present invention claims the priority and rights of U.S. Provisional Patent Application No. 62 / 417,865 filed on November 4, 2016 and U.S. Provisional Patent Application No. 62 / 417,891 filed on November 4, 2016. Its entire content is incorporated herein. [0002] References to Electronically Submitted Sequence Listings [0003] The present application incorporates by reference the Sequence Listing filed with the present application as a text file titled "13194-025-228_ST25.TXT", which was generated on October 31, 2017 and is 113 kilobytes in size . [0004] 1 Introduction [0005] The present application generally relates to genetically modified arenaviruses as suitable vaccines against neoplastic diseases, such as cancer. The arenaviruses described herein may be suitable as vaccines and / or for the treatment of neoplastic diseases and / or for use in immunotherapy. In particular, provided herein are methods and compositions for treating neoplastic...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K39/12
CPCA61K39/12A61K2039/572A61K2039/585C12N2710/20034C12N2760/10043A61P35/00A61K39/001156A61K39/001192A61P31/00
Inventor 莎拉·施密特克劳斯·奥尔林格桑德拉·斯蒂芬妮·林卢卡斯·罗兰·弗拉茨
Owner HOOKIPA BIOTECH GMBH
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