CD38 protein antibody and application thereof

An antibody and protein technology, applied in the direction of antibodies, applications, immunoglobulins, etc., can solve the problems of limited cytotoxic activity, limited CD38 antibody recognition activity, limited tumor inhibitory ability, etc., and achieve the effect of inhibiting tumor growth.

Active Publication Date: 2019-08-20
HANGZHOU SUMGEN BIOTECH CO LTD +1
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0003] However, the currently developed CD38 antibodies have limited recognition activity, limited cytotoxic activity, and limited ability to inhibit tumors. Therefore, it is urgent to develop new CD38 antibodies for new drug development

Method used

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  • CD38 protein antibody and application thereof
  • CD38 protein antibody and application thereof
  • CD38 protein antibody and application thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment approach

[0130] 1. Antibodies, antigen-binding fragments or variants thereof, in 1×10 -9 M or lower K D Binds to CD38 protein.

[0131] 2. The antibody, antigen-binding fragment or variant thereof according to embodiment 1, which can kill tumor cells and / or inhibit tumor growth by specifically binding to CD38 protein.

[0132] 3. The antibody, antigen-binding fragment or variant thereof, according to any one of embodiments 1-2, which is capable of passing antibody-dependent cell-mediated cytotoxic ADCC, complement-dependent cytotoxic CDC and / or apoptosis kill CD38 + cell.

[0133] 4. The antibody, antigen-binding fragment or variant thereof of embodiment 3, wherein said tumor comprises a CD38 positive tumor.

[0134] 5. The antibody, antigen-binding fragment or variant thereof according to embodiment 4, wherein said CD38 positive is selected from the group consisting of multiple myeloma, lymphoma and leukemia.

[0135] 6. The antibody, antigen-binding fragment or variant thereof, ...

Embodiment 1

[0188] Embodiment 1 Hybridoma antibody preparation and gene cloning

[0189] Mouse immunization: balb / c mice (purchased from Beijing Weitong Lihua Experimental Animal Technology Co., Ltd.) were subcutaneously (s.c.) mixed with 100 μg of soluble CD38 antigen (purchased from Beijing Yi Qiao Shenzhou Biotechnology Co., Ltd.) immune 3 times. Freund's complete adjuvant was used on day 0, and Freund's incomplete adjuvant was used on day 14 and 28. Splenocytes from immunized mice were fused with mouse myeloma cells SP2 / 0 (ATCC) according to standard methods.

[0190] Hybridoma fusion: Fusion mouse spleen according to the existing conventional hybridoma fusion method, HAT screening method to screen the fused hybridoma cells (10 per well 5 cells). After 12 days, the supernatant was taken and detected by ELISA on a CD38 antigen-coated microtiter plate. Preferred clones were subjected to a second round of subcloning by limiting dilution. After the hybridoma strain stably expressing ...

Embodiment 2

[0192] Example 2 Transformation and preparation of antibody humanization

[0193] On the basis of obtaining the heavy and light chain sequences of the murine antibody variable regions in Example 1, the online sequence alignment method (IgBlast) provided by NCBI is compared with the existing human antibody sequences in the NCBI database to determine the potential human origin The humanization site was further constructed by SwissModel to construct the three-dimensional structure of the variable region of the murine antibody, and the humanization site was determined; for the corresponding humanization site, humanization transformation was carried out to obtain the sequence of the humanized antibody.

[0194]The humanized antibody was named SG003, and the sequencing results showed that the amino acid sequences of LCDR1-3 of the antibody SG003 are shown in SEQ ID NO.1, SEQ ID NO.2 and SEQ ID NO.3 respectively; the amino acid of VL The sequence is shown in SEQ ID NO.7; the nucleoti...

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Abstract

The application relates to an antibody, and an antigen binding fragment or variant thereof. The antibody at the K<D> value being 1*10<-9>M or below is combined with CD38 protein. The antibody or the antigen binding fragment thereof has high specific recognition combining capacity on the CD38 protein, and can kill CD38<+> cells through antibody-dependent cell-mediated cytotoxicity ADCC, complement-dependent cytotoxicity CDC and / or apoptosis. The application also provides an application of the antibody and the antigen binding fragment or variant thereof to tumor prevention and treatment.

Description

technical field [0001] This application relates to the field of biomedicine, in particular to an antibody capable of binding to CD38 protein. Background technique [0002] CD38 protein can catalyze NAD + A bifunctional exonuclease that converts to cyclic ADP-ribose (cADPR, cyclic ADP-ribose) and hydrolyzes cADPR to ADP-ribose. Normally, CD38 is expressed by hematopoietic cells and solid tissues. Most medullary thymocytes are CD38 + , resting and circulating T and B cells as CD38 - , activated cells are CD38 + . CD38 protein is one of the antigens expressed on malignant plasma cells, and is expressed in various malignant blood disease cells, including but not limited to multiple myeloma cells, B-cell chronic lymphocytic leukemia cells, and B-cell acute lymphoblastic leukemia cells. From a functional point of view, CD38 protein is involved in receptor-mediated activities such as adhesion, signal transmission, and external (ecto-) enzyme activity. CD38 has a variety of c...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07K16/28C12N15/13C12P21/00A61K39/395A61P35/00A61P35/02
CPCC07K16/2896C07K2317/24C07K2317/33C07K2317/56C07K2317/732C07K2317/734C07K2317/73C07K2317/92A61K2039/505A61P35/00A61P35/02C07K2317/76C07K2317/565C07K2317/51C07K2317/515C12N5/10A61K48/00A61K31/713C12N15/63
Inventor 吕明
Owner HANGZHOU SUMGEN BIOTECH CO LTD
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