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Guanabenz as an adjuvant for immunotherapy

An immunotherapy, guanabenz technology, applied in the field of cancer immunotherapy and immunotherapy, can solve the problem of limited overall efficacy of immunotherapy

Pending Publication Date: 2021-08-27
UNIVERSITE CATHOLIQUE DE LOUVAIN
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0010] However, the overall efficacy of immunotherapy remains limited in most patients (Jenkins et al., 2018, Br J Cancer 118, 9-16; Ladanyi. 2015, Pigment Cell Melanoma Res 28, 490-500)

Method used

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  • Guanabenz as an adjuvant for immunotherapy
  • Guanabenz as an adjuvant for immunotherapy
  • Guanabenz as an adjuvant for immunotherapy

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0341] Materials and Methods

[0342] Material

[0343] mouse

[0344] TiRP mice: Ink4a / Arf flox / flox Mice were crossed with mice carrying a transgenic construct controlled by a tyrosinase promoter and driving Trap1a and H-Ras encoding the MAGE-type tumor antigen P1A 12V to generate TiRP mice; the promoter was separated from the coding region by a termination cassette made of floxed self-deletion CreER (Huijbers et al., 2006, Cancer Res 66, 3278-3286). Those mice were backcrossed to the B10.D2 background and bred to homozygosity. TCRP1A mice heterozygous for the H-2Ld / P1A35-43-specific TCR transgene were maintained at B10.D2;Rag1 - / - Background (Shanker et al., 2004, J Immunol 172, 5069-5077). All mice used in this study were generated under specific pathogen-free (SPF) conditions at the animal facility of the Ludwig Institute for Cancer Research. All rules regarding animal welfare have been complied with according to Directive 2010 / 63 / EU. All procedures were performe...

Embodiment 2

[0372] Materials and Methods

[0373] Material

[0374] mouse

[0375] DBA / 2 mice and C57BL / 6J mice were used in the immunization experiments.

[0376] method

[0377] immunity

[0378] Immunization with irradiated L1210-P1A-B7.1 tumor cells: DBA / 2 mice received a vaccine consisting of one million irradiated L1210-P1A-B7.1 cells expressing the P1A antigen alone Or consist of it together with 100 μg (5 mg / kg) guanabenz. When administered, guanabenz was given 1 hour before immunization and daily after immunization. Include unimmunized mice as negative controls.

[0379] Immunization with ovalbumin: C57BL / 6J mice were immunized once by intraperitoneal (i.p.) injection of 200ug OVA protein adsorbed on aluminum hydroxide adjuvant 2% (Sigma). These mice were administered 100 μg (5 mg / kg) of guanabenzine 2 hours before immunization and daily after immunization. Include unimmunized mice as negative controls.

[0380] Evaluate the immune response

[0381] Intracellular ...

Embodiment 3

[0391] Materials and Methods

[0392] Material

[0393] mouse

[0394] Sex- and age-matched CD57BL / 6 wild-type mice were used in the B16F10-transplanted melanoma model.

[0395] method

[0396] Tumor induction and mouse treatment

[0397] One million B16F10 tumor cells were injected subcutaneously into sex-matched, 7- to 9-week-old CD57BL / 6 wild-type mice. One week after tumor cell injection, mice were randomized based on tumor size. Seven days after tumor inoculation, mice were administered daily guanabenz (2.5 mg / kg, i.p.) or vehicle (PBS, i.p.) injections. The mice then received 4 doses of 200 μg / mouse of anti-PD-1 antibody (BioXcell, clone RMP1-14) or RatIgG2a isotype (clone 2A3, Bio-X-Cell) injection (intraperitoneal, also called i.p.).

[0398] result

[0399] The effect of guanabenz in combination with a PD-1 inhibitor on tumor growth was assessed in B16F10-transplanted melanoma-bearing mice.

[0400] like Figure 9 It was shown that administration of anti...

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Abstract

The present invention relates to guanabenz for use with an immunotherapy in the treatment of a cancer or of an infectious disease. In particular, guanabenz is used as an adjuvant for an immunotherapy, such as a cancer immunotherapy or a vaccination. The present invention relates more specifically to guanabenz for use with an adoptive cell therapy, with a therapeutic vaccine, with a checkpoint inhibitor therapy or with a T-cell agonist therapy in the treatment of a cancer. The present invention also relates to guanabenz for use with a vaccination in the prophylactic and / or therapeutic treatment of an infectious disease.

Description

technical field [0001] The present invention relates to the field of immunotherapy, especially cancer immunotherapy. More specifically, the present invention relates to the use of guanabenz as an adjuvant in immunotherapy. [0002] Background of the invention [0003] Immunotherapy can be broadly defined as a therapy aimed at inducing and / or enhancing an immune response against a specific target, for example against infectious agents such as viruses, bacteria, fungi or protozoan parasites or against cancer cells. To improve its therapeutic effect, immunotherapy is often administered in combination with adjuvants. Adjuvant compounds thus seek to potentiate or modulate the immune response against a particular target, in particular to enhance, accelerate and / or prolong said immune response. [0004] In recent years, immunotherapy has proven to be one of the most promising advances in cancer treatment. Cancer immunotherapy manipulates a subject's immune system with the aim of ...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K31/155A61K45/00A61P31/00A61P31/04A61P31/10A61P31/02A61P35/00A61P31/12
CPCA61K31/155A61K45/00A61P31/00A61P31/02A61P31/04A61P31/10A61P31/12A61P35/00A61K39/0011A61K39/4644A61K2239/31A61K39/46449A61K39/464838A61K2239/38A61K39/4646A61K39/4611A61K39/464453A61K39/4622A61K2300/00A61K39/39A61K45/06A61K2039/55511A61K2039/505
Inventor B·范登艾恩德朱晶晶
Owner UNIVERSITE CATHOLIQUE DE LOUVAIN