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Peptides in combination with immune checkpoint inhibitors for use in treatment of cancer

A technology of immune checkpoints and inhibitors, applied in the direction of anti-animal/human immunoglobulin, drug combination, immunoglobulin, etc., can solve the problem of high toxicity of patients

Pending Publication Date: 2022-01-14
ウィントリサーチアーベー
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

A disadvantage of this type of therapy is that combination therapy can be more toxic to patients than monotherapy

Method used

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  • Peptides in combination with immune checkpoint inhibitors for use in treatment of cancer
  • Peptides in combination with immune checkpoint inhibitors for use in treatment of cancer
  • Peptides in combination with immune checkpoint inhibitors for use in treatment of cancer

Examples

Experimental program
Comparison scheme
Effect test

example 1

[0064] Example 1 (Scheme LEV 197)

[0065] Objective: To analyze the immune responses against cancer antigens induced in BALB / c mice following tumor challenge and treatment with immunotherapy. Animals were purchased from Envigo, 6-8 weeks old, and allowed to rest for 1 week or more after arrival before entering experiments.

[0066] Table 1 Groups:

[0067] mouse vaccination program termination A 5 Tumor, PBS Tumor challenge (4T1-Luc) B 5 Tumor, PD-L1, CTLA-4 Tumor challenge (4T1-Luc) C 5 Tumor, Foxy-5 Tumor challenge (4T1-Luc) D 5 Tumor, PD-L1, CTLA-4, Foxy-5 Tumor challenge (4T1-Luc)

[0068] • Tumor challenge: Day 0: 5*10^4 4T1-Luc cells in 100uL S.C.

[0069] Foxy-5 injection (i.p., 100ul, 40ug / mouse): Day 0, 4, 8, 12, 16 -> total 200ug / mouse

[0070] When most tumors are palpable: Inject PD-L1 (BioXcell BE0146) and CTLA-4 (BioXcell BE0164) (i.p., 100ul):

[0071] οThe first injection: PD-L1-200ug / CTLA4-200ug

...

example 2

[0076] Example 2 (Scheme LEV 221)

[0077] Objective: To analyze the immune response against cancer antigens induced after tumor challenge and treatment with immunotherapy in BALB / c mice

[0078] Table 2: Groups:

[0079]

[0080]

[0081] • Tumor challenge: Day 0: 5*10^5 4T1 cells in 100uL S.C.

[0082] Foxy-5 injection (i.p., 100u1, 40ug / mouse): Day 0, 4, 8, 12, 16 -> a total of 200ug / mouse is required

[0083] Injection of PD-L1 (BioXcell BE0146) and CTLA-4 (BioXcell BE0164) (i.p., 100ul) on days 8, 12 and 16:

[0084] οThe first injection: PD-L1-200ug / CTLA4-200ug

[0085] οThe second injection: PD-L1-200ug / CTLA4-100ug

[0086] οThe third injection: PD-L1-200ug / CTLA4-100ug

[0087] • Mice were euthanized on day 17.

[0088] see results Figure 2a -d. Conclusions: Implantation of high doses of 4T1luc cells resulted in a significant reduction in tumor growth in the PD-L1- and CTLA-4 inhibitor-treated groups (p<0.05 in the last two measurements), but most surpris...

example 3

[0089] Example 3 (respectively image 3 with Figure 4 )

[0090] Objective: The ability of a WNT5A agonist (expressed as Foxy-5) in this context to reduce PD-L1 and CD47 expression on the cell surface of breast and colon cancer cells was examined. It is well established that the antiphagocytic cell surface molecule CD47 that produces the "don't eat me signal" is widely overexpressed in multiple tumor types.

[0091] The relationship between WNT5A signaling and CD47 expression was initiated in the triple-negative and WNT5A-negative breast cancer cell line 4T1. The results showed that the massive CD47 expression in these cells was significantly reduced after Foxy-5 stimulation (24h, n=4).

[0092] Next investigated how Foxy-5 might affect PD-L1 expression in 4T1 cells. Unstimulated 4T1 cells in tissue culture were observed to express limited amounts of PD-L1. Therefore, prestimulation (6h) was performed with interferon gamma (IFNγ), a known inducer of PD-L1 in cancer cel...

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PUM

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Abstract

A WNT5A peptide or derivatives thereof in combination with one or more checkpoint inhibitors for use in treatment of cancer in a subject in need thereof. Furthermore, WNT5A peptides or derivatives thereof may be used in treatment of cancer in a subject, wherein the subject is responsive to immune checkpoint inhibitors.

Description

technical field [0001] A WNT5A peptide or derivative thereof for use in the treatment of cancer in a subject responsive to a checkpoint inhibitor. Background technique [0002] The link between the immune system and cancer has long been appreciated. The immune system defends and protects individuals by detecting "non-self" and overexpressed antigens from pathogens or infected / malignant cells; targeting and destroying pathogens or infected / malignant cells while protecting the host; Generates immune memory for subsequent defense mechanisms. [0003] A checkpoint inhibitor (ICI) is a type of drug that blocks so-called immune checkpoints. Immune checkpoint ligands appear on the surface of tumor cells and immune dampening immune cells, while cognate molecules appear on the surface of tumor-reactive immune system cells such as T cells and natural killer cells. These molecules help weaken the immune response and prevent overactivation of the immune system. When cancer-specific ...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K38/00A61K38/17A61K39/395A61P35/00C07K16/28A61K39/00
CPCC07K16/2827A61K2039/505A61K38/00A61K39/395C07K2317/76A61K38/1709A61P35/00A61K38/17C07K7/06C07K7/08C07K16/2818A61K38/08A61K38/10A61K2300/00A61K38/18A61K39/3955
Inventor 彼得·约翰尼斯·霍尔斯特莱纳·阿克塞尔松汤米·安德森
Owner ウィントリサーチアーベー
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