Nuclide-labeled PD-1-targeted monoclonal antibody and preparation method and application thereof

A monoclonal antibody, PD-1 technology, applied in the field of nuclear medicine, can solve the problems of inability to provide PD-1 and PD-L1 expression information, complex immunohistochemical detection, inability to monitor expression levels, etc., and achieve good in vitro stability. Sex, to achieve individualized, high-affinity effects

Inactive Publication Date: 2020-07-10
BEIJING CANCER HOSPITAL PEKING UNIV CANCER HOSPITAL
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

As a classic method, immunohistochemical method still has some shortcomings: (1) immunohistochemical method is an invasive method, which needs to take specimens to make pathological sections; some tumors are not suitable for biopsy, so immunohistochemical method cannot be used Detection of PD-1 and PD-L1 expression by chemical method
(2) The results of immunohistochemistry are only the expression levels of PD-1 and PD-L1 in pathological sections, and cannot provide information on the expression of PD-1 and PD-L1 in the whole body and in distant metastasis
(3) The detection of immunohistochemical method is relatively complicated, and the expression levels of PD-1 and PD-L1 cannot be monitored for the treatment process and prognosis

Method used

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  • Nuclide-labeled PD-1-targeted monoclonal antibody and preparation method and application thereof
  • Nuclide-labeled PD-1-targeted monoclonal antibody and preparation method and application thereof

Examples

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Embodiment 1

[0041] Example 1 Preparation of novel radionuclide-labeled PD-1 targeting monoclonal antibody (1)

[0042] This example provides 124 I mark Toripalimab ( 124 I-Toripalimab) and preparation method thereof. 124 I-Toripalimab is prepared by NBS reaction, and the specific preparation method is as follows:

[0043] To 0.7ml, 45KBq / μL Na 124 Add 0.5ml of 0.1M PB buffer (pH7.2), 0.1mL, 10mg / mL of Toripalimab monoclonal antibody solution (prepared with water for monoclonal antibody solution) and 12 μg of N-bromosuccinimide (NBS) in the I solution , reacted at 37°C for 1min, and added 10% human serum albumin (HSA) to terminate the reaction; the reaction solution was purified by a PD-10 prepacked gel column to obtain the target product 124 I - Toripalimab.

[0044] Before use, the PD-10 prepacked gel column needs to be equilibrated with 0.01M PBS buffer of pH 7.4, add 5 mL each time, flow dry at a gravity flow rate, and repeat 5 times; then use 0.01M PBS buffer of pH 7.4 Purificat...

Embodiment 2

[0045] Example 2 Preparation of novel radionuclide-labeled PD-1 targeting monoclonal antibody (2)

[0046] This example provides 64 Cu marked Toripalimab ( 64 Cu-Toripalimab) and its preparation method. 64 Cu-Toripalimab is prepared through a bifunctional chelating agent coupling reaction, and the specific preparation method is as follows:

[0047] Add DFO equivalent to 6 times the molar equivalent of toripalimab monoclonal antibody to 1ml of toripalimab solution with a concentration of 2mg / ml, adjust the pH value of the reaction system to 8.5 with deionized 0.1M sodium bicarbonate solution; react at 37°C After 24 hours, the labeled precursor DFO-Toripalimab was obtained. Take 2 mg of the labeled precursor, add it to 1.0 ml of 0.1 M sodium acetate solution at pH 5.5, and then add 74 MBq of freshly prepared 64 Cu solution, adjust the pH to 7.0, and incubate at 40°C for 30 minutes; the resulting reaction solution is separated and purified by a PD-10 column to obtain the targ...

Embodiment 3

[0049] Example 3 Preparation of novel radionuclide-labeled PD-1 targeting monoclonal antibody (3)

[0050] This example provides 89 Zr marks Toripalimab ( 89 Zr-Toripalimab) and its preparation method. 89 Zr-Toripalimab is prepared through a bifunctional chelating agent coupling reaction, and the specific preparation method is as follows:

[0051] Add DFO equivalent to 6 times the molar equivalent of toripalimab monoclonal antibody to 1ml of toripalimab solution with a concentration of 2mg / ml, adjust the pH value of the reaction system to 8.5 with deionized 0.1M sodium bicarbonate solution; react at 37°C After 24 hours, the labeled precursor DFO-Toripalimab was obtained. Take 2 mg of the labeled precursor, add it to 1.0 ml of 0.1 M sodium acetate solution at pH 5.5, and then add 74 MBq of freshly prepared 89 Zr solution, adjust the pH to 7.0, and incubate at 40°C for 30 minutes; the resulting reaction solution is separated and purified by a PD-10 column to obtain the targe...

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Abstract

The invention relates to the technical field of nuclear medicine, in particular to a nuclide-labeled PD-1-targeted monoclonal antibody and a preparation method and application thereof. The preparationmethod comprises the steps: mediating a PD-1 monoclonal antibody through N-bromosuccinimide, or coupling the PD-1 monoclonal antibody with a bifunctional chelating agent deferoxamine, and then performing labeling with 124I, 64Cu or 89Zr radionuclide so as to obtain the nuclide-labeled PD-1 monoclonal antibody. The labeled monoclonal antibody has a high labeling rate, high purity, high in-vitro stability, high affinity and specificity to PD-1, high functional activity for PD-1 and a good imaging effect, uptake by PD-1 positive tumors is high, non-specific uptake by livers is low, detection ofliver lesions is facilitated, the whole body background is low, and a good tumor-to-non-tumor ratio is obtained; and the labeled monoclonal antibody can be applied to diagnosis and treatment of PD-1 high-expression tumors, and individualized and precise treatment is achieved through tumor-targeted drugs.

Description

technical field [0001] The invention relates to the technical field of nuclear medicine, in particular to a radionuclide-labeled PD-1 targeting monoclonal antibody and a preparation method and application thereof. Background technique [0002] Programmed cell death molecule-1 (PD-1) and its ligand PD-L1 are currently the most widely used immunosuppressive points in clinical practice. In many clinical trials, anti-PD-1 or PD-L1 monoclonal antibodies have achieved therapeutic effects far exceeding expectations in patients with a variety of refractory and recurrent tumors. Therefore, the US FDA quickly approved the anti-PD-1 monoclonal antibodies pembrolizumab, nivolumab and anti-PD-L1 monoclonal antibodies durvalumab, atezolizumab, avelumab, these monoclonal antibodies have become the standard treatment for a variety of tumors. [0003] Studies have shown that not all tumor patients respond to monoclonal antibodies in the PD-1 and PD-L1 pathways, and anti-PD-1 / PD-L1 monoclona...

Claims

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Application Information

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IPC IPC(8): A61K51/10A61K47/68C07K16/28C07K1/13A61K101/02A61K103/00
CPCA61K51/1027A61K47/6849A61P35/00C07K16/2818
Inventor 杨志王淑静朱华丁缙王风丁立新
Owner BEIJING CANCER HOSPITAL PEKING UNIV CANCER HOSPITAL
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