Combinations for immune-modulation in cancer treatment

A technology of cancer and immune memory, applied in the field of cancer treatment

Pending Publication Date: 2021-06-22
SENHWA BIOSCIENCES INC
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

However, CK2 inhibitors alone may have only moderate anticancer effects against certain cancer types

Method used

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  • Combinations for immune-modulation in cancer treatment
  • Combinations for immune-modulation in cancer treatment
  • Combinations for immune-modulation in cancer treatment

Examples

Experimental program
Comparison scheme
Effect test

example 1

[0095] Example 1 CX-4945 exhibits in vivo synergy with the DNA damaging agent gemcitabine

[0096] In the A2780 ovarian tumor model, gemcitabine (Gem) (120 mg / kg) and CX-4945 (25 mg / kg or 100 mg / kg) ( figure 1 ) combination showed a significant increase in endpoint time. The Colo-205 colorectal cancer model is resistant to individual agents alone ( figure 2 ). However, the combination of gemcitabine and CX-4945 significantly reduced tumor growth, suggesting that the combination may be effective in indications for which gemcitabine alone has not been approved.

example 2

[0097] Example 2 Utilizes medicine combination to enhance anti-tumor effect in cancer animal model

[0098] Table 1 shows that the pharmaceutical combinations described in the present invention produce synergistic antitumor effects in vivo. The use of gemcitabine at 60 mg / kg iv and 100 mg / kg orally administered to A2780 ovarian cancer xenografts with CX-4945 was well tolerated and significantly enhanced antitumor activity compared to gemcitabine alone. Time to endpoint (TTE) analysis showed a significant delay in time to endpoint for gemcitabine, CX-4945, and the combination of the two agents.

[0099] Table 1

[0100]

[0101]

[0102] *CR: Complete Response

[0103] **PR: partial response

example 3

[0104] Example 3 CX-4945 significantly increases T cells in tumors and synergistically inhibits tumor growth in vivo with chemotherapeutic agents

[0105] Tumor growth inhibition and T cell activation in the immunocompetent syngeneic mouse model 4T1 (i.e., known to be resistant to treatment with immune checkpoint inhibitors such as anti-PD1, anti-PD-L1, and anti-CTLA4) efficacy research. Resistance to these antagonists that modulate T cell co-stimulatory signaling is indicative of a highly immunosuppressive tumor microenvironment.

[0106] This series of studies was performed in six to eight week old Balb / C mice. with 3 x 10 5 Breast cancer cell 4T1 cells were subcutaneously injected into the right flank of mice in 0.1 ml PBS. When the average tumor size reaches approximately 80-120mm 3 , the mice were randomized for treatment. Treatment with CX-4945 and / or cisplatin was administered at the doses and schedules described in Table 1. Prepare CX-4945 in 25mM Na 2 HPO 4 so...

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Abstract

The present disclosure provides a method for treating a cancer or refractory caner and / or inhibiting cancer metastasis, recurrence or progression in a subject or increasing the likelihood of survival over a relevant period in a subject diagnosed with a cancer, comprising administering to a subject a combination of an anti-cancer agent, a CK2 inhibitor and optionally an immune checkpoint inhibitor. The method of the present disclosure increases the number of T cells and activated T cells in the tumor microenvironment and thus can modulate immune in cancer therapy.

Description

technical field [0001] The present invention relates to the field of cancer treatment. In particular, the invention provides a method of treating cancer using a combination of a chemotherapeutic agent, a CK2 inhibitor, and an immune checkpoint inhibitor. Background technique [0002] The protein kinase CK2 is upregulated in many human cancers and is therefore considered a target for cancer therapy (Chua et al., Pharmaceuticals 2017, 10, 18). CK2 inhibitors have been shown to inhibit cell proliferation and are useful in the treatment of neoplastic disorders such as breast, prostate, pancreatic, lung, hematopoietic, colorectal, skin and ovarian cancers (Chua et al., US 9,062,043 B2 ). However, CK2 inhibitors alone may have only moderate anticancer effects against certain cancer types. [0003] Several series of CK2 inhibitors have been studied for their activity in inhibiting cell growth alone and in combination with other antiproliferative agents (patents US9,062,043B2, US...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K31/5025A61K31/50C07D237/00C07D487/04
CPCA61K45/06A61P35/00A61K31/7068A61K33/243A61K31/4375A61P35/04A61K39/39558C07K16/2818A61K2039/505A61K2300/00A61K31/4738C07D471/04
Inventor 宋佳恩
Owner SENHWA BIOSCIENCES INC
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