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Association of polyclonal antibodies and Anti-pd1 or Anti-pdl1 antibodies for the treatment of cancer

A polyclonal antibody, monoclonal antibody technology, applied in the field of immunology

Pending Publication Date: 2021-12-14
XENOTHERA
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

In fact, in such tumors, the response rate to therapeutic monoclonal antibodies targeting immune checkpoints commonly used in therapeutic antibodies (such as the treatment of tumors) remains relatively low and thus ineffective

Method used

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  • Association of polyclonal antibodies and Anti-pd1 or Anti-pdl1 antibodies for the treatment of cancer
  • Association of polyclonal antibodies and Anti-pd1 or Anti-pdl1 antibodies for the treatment of cancer
  • Association of polyclonal antibodies and Anti-pd1 or Anti-pdl1 antibodies for the treatment of cancer

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0185] Example 1: ELISA control of polyclonal antibodies obtained by immunizing rabbits with cancer cell lines

[0186] Rabbits were immunized with cells from the murine tumor cell line Hepa 1.6 (hepatocellular carcinoma) to obtain the corresponding anti-tumor polyclonal antibodies.

[0187] The tumor cells were subcutaneously injected twice with an interval of two weeks.

[0188] 7 days after the first subcutaneous injection (Rabbit–I1+7) and 7 days after the second subcutaneous injection (Rabbit–I2+7), sera were actually collected in pre-immunized rabbits (Rabbit–J0) for testing The ability of the antibodies to recognize tumor cells used to immunize rabbits.

[0189] More specifically, the antibody response of the immunized rabbits was measured using a cellular ELISA assay based on the Hepa 1.6 cells used to immunize the rabbits. The collected serum was serially diluted 1:20; 1:60; 1:180; 1:540; 1:1620; 1:4860; 1:14580; Incubate for 2 hours at room temperature. After t...

Embodiment 2

[0193] Example 2: In vivo use of pooled polyclonal antibodies in syngeneic and orthotopic mouse models

[0194] The Hepa1.6 hepatocellular carcinoma mouse model has been used and described in Gauttier et al., Int J Cancer. 2014 Dec 15;135(12):2857-67.

[0195] This model is syngeneic and in situ in immunocompetent C57 / BL6J mice.

[0196] 2.5.10 resuspended in PBS 6 Individual Hepa1.6 cells were injected into the portal vein of 8-week-old male mice, which, if left untreated, resulted in hepatic hypertension and death of the animals within 12-15 days.

[0197] Four days later (D4) different treatments were administered:

[0198] - Group 1 (Group 1; n=7; Control), receiving: control isotype (3G8: irrelevant monoclonal antibody (mAb) - isotype IgG1) (8 mg / kg, 2 times a week, 28 days) + rabbit polyclonal antibody before immunization (20mg / kg, 2 times a week, 28 days).

[0199] - Second group (group 2; n=8; comparison), receiving: control isotype (3G8: irrelevant monoclonal an...

Embodiment 3

[0215] Example 3: Polyclonal antibodies of the invention allow conversion of cold tumors to hot tumors

[0216] Rabbits were immunized with mouse B16F10 melanoma cells to obtain corresponding anti-tumor polyclonal antibodies.

[0217] It is well known that the B16F10 melanoma cell line is a good example of a "cold" tumor because, for example, it is resistant to anti-PDL1 antibodies, where such antibodies have very limited effect on tumor regression (Chen et al., Cancer Immunol res. 2014; 3(2):149-60; Ueha et al., 2015; 3(6):631-40).

[0218] These IgG fractions of polyclonal antibodies raised against B16F10 cells from rabbits were infused into subcutaneous implants every two weeks (12.5 mg / kg twice a week) from day 4 (D4) to day 30 (D30) B16F10 melanoma cells (D0) in Balb / C mice (Group 2 - n=8).

[0219] The same animal control group (group 1-n=7) subcutaneously implanted with B16F10 melanoma cells received only rabbit polyclonal antibody (20 mg / kg, twice a week, 28 days) ...

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Abstract

The present invention relates to an association of non-human mammal polyclonal antibodies directed against cancer cells; and at least one monoclonal antibody selected from the group consisting of anti-PD1 and anti-PDL1 monoclonal antibodies for its use for preventing and / or treating a cancer in a mammal patient. The association as such is also considered.

Description

technical field [0001] The present invention relates to the field of immunology, and more particularly to combinations of polyclonal antibodies with monoclonal anti-PD1 and / or anti-PDL1 antibodies, and their use in human medicine. [0002] In particular, the invention relates to the use of polyclonal non-human mammalian antibodies in combination with monoclonal anti-PD1 and / or anti-PDL1 antibodies in the treatment of cancer. Background technique [0003] Cancer is the second leading cause of death in the world and an estimated 9.6 million people died from cancer in 2018. Globally, cancer is responsible for approximately one in six deaths worldwide. Unavailable or insufficiently active treatment is common in this field. Accordingly, there is a recognized need for the development of new and improved therapies for the treatment of cancer. [0004] Immunotherapy represents real hope for the treatment of a large number of cancers, especially those that cannot currently be effe...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07K16/30C07K16/28A61P35/00
CPCC07K16/3076C07K16/2818C07K16/2827A61P35/00A61K2039/507C07K2317/41
Inventor O·迪沃B·瓦恩霍维
Owner XENOTHERA