Antibodies targeting cd3, bispecific antibodies and uses thereof

Abstract

The invention discloses an antibody targeting CD3, a bispecific antibody and application thereof. The antibody targeting CD3 comprises a light chain variable region (VL) and a heavy chain variable region (VH), and the VL is the amino acid sequence shown in SEQ ID NO: 56 or a mutation thereof; the VH is in A mutation occurs in the amino acid sequence as shown in SEQ ID NO: 42, and the mutation is selected from one or more of the following positions: 30th, 73rd, 76th, 78th, 93rd and 94th amino acid residues. The bispecific antibody includes a first protein functional region and a second protein functional region, wherein the first protein functional region comprises the antibody targeting CD3 as described above. The CD3-targeting antibody of the present invention reduces the toxicity caused by cytokine release syndrome, and the bispecific antibody prepared therefrom is stable and has T cell binding ability, which reduces production difficulty.

Description

[0001] This application claims the priority of Chinese patent application 2019109413286 with a filing date of 2019 / 9 / 30. This application cites the full text of the above-mentioned Chinese patent application. technical field [0002] The invention relates to the field of biopharmaceuticals, in particular to a CD3-targeting antibody, a bispecific antibody and uses thereof. Background technique [0003] T lymphocytes are an important class of cells involved in the adaptive immune response, and T cells recognize antigens through the T cell receptor (TCR). TCR does not directly recognize antigen surface epitopes, but specifically recognizes antigen peptide-MHC molecular complexes (pMHC) presented on the surface of antigen-presenting cells (APC) or target cells. The specificity of T cell responses is mediated by the recognition of pMHC by the molecular complex of TCR and CD3. TCR is a heterodimer composed of two different transmembrane polypeptide chains. There are four types o...

AI Technical Summary

Problems solved by technology

Second, the affinity of the CD3 antibody to the CD3 complex is also very important. A CD3 antibody with too high affinity may limit the antibody to the spleen and other parts, making it difficult to reach the tumor; and too high affinity may also over-stimulate T cells to bring high levels cytokine release

Third, CD3 antibody binding valence also has an important impact. It was previously found that multivalent forms of CD3 bispecific antibodies may activate T cells without binding tumor-associated antigens and cause side effects. Therefore, most CD3 bispecific antibodies under research Sexual antibodies are in the form of monovalent CD3

In order to construct the BsTCE bispecific antibody, the inventors tried to convert the SP34 mouse anti-IgG into scFv, but no matter which (VH / VL) arrangement mode was adopted or the length of the connecting peptide was changed, a stable scFv could not be obtained. The field urgently needs a stable anti-CD3 monoclonal antibody, especially its stable scFv structure

Images