Anti-B7-H7 antibody or antigen-binding fragment thereof, and production method and application

Abstract

The present invention discloses an anti-B7-H7 antibody or an antigen-binding fragment thereof, and a method for producing and applying the same, the antibody comprising a VL and / or a VH, the VL comprising CDRs LCDR1, LCDR2 and LCDR3 shown in the amino acid sequences of SEQ ID NO:82, SEQ ID NO:94-100, SEQ ID NO:111, 112, 114-116, 120 and 121 or mutations thereof, and the VH comprising CDRs HCDR1, HCDR2 and HCDR3 shown in the amino acid sequences of SEQ ID NO:7, SEQ ID NO:34 or 36, SEQ ID NO:57-68 or mutations thereof. The anti-B7-H7 antibody or its antigen-binding fragment described in the present invention has high affinity and high biological activity for B7-H7, can effectively block the binding of B7-H7 to its receptor CD28H and the binding of B7-H7 to its receptor KIR3DL3, and it specifically binds only to B7-H7, does not cross-react with other member proteins of the B7 family, has excellent stability, and yet exhibits high in vivo anti-tumor activity.

Description

[Technical field]

[0001] This international patent application claims priority to Chinese Patent Application No. 202210071861.3 filed on January 21, 2022, the contents of which are incorporated herein by reference in their entirety.

[0002] The present invention relates to the field of biomedicine, in particular to an anti-B7-H7 antibody or an antigen-binding fragment thereof, and a method for producing the same and its application. [Background technology]

[0003] In the tumor microenvironment, immune checkpoint molecules are often highly expressed, promoting tumor evasion immune system attacks by inhibiting T cell activation and inducing T cell exhaustion. Immune checkpoint inhibition is the most advanced therapeutic method that has achieved the best therapeutic effects in current anti-tumor immunotherapy. For example, anti-PD1, PD-L1, and CTLA-4 immune checkpoint inhibitors have shown strong anti-tumor activity clinically. Therefore, the 2018 Nobel Prize in Physiology or Medicine honored two scientists who discovered PD1 and CTLA-4 negative immune regulation and made great contributions to cancer treatment.

[0004] Clinically, anti-PD1, PD-L1, and CTLA-4 treatments have achieved good therapeutic effects, but the response rate of patients is not high, and most patients are resistant to treatment with these targets or have normal therapeutic effects. The tumor microenvironment has been proven to be a very complex and comprehensive mechanism, with multiple immune inhibitory molecules, suppressor cells, and special tumor tissue structures working together to block the development of normal immune responses, making it difficult to achieve good therapeutic effects by only blocking one immune checkpoint. In addition to these PD1, PD-L1, and CTLA-4 targets, other immune checkpoints, such as Tim3, Lag3, and TIGIT, are also highly expressed in the tumor microenvironment. Currently, research into these immune checkpoints has shown that inhibiting these targets or combining them with anti-PD1 / PD-L1 antibodies can further enhance the therapeutic effect of anti-tumor therapy.

[0005] The B7 family is an important immune system costimulatory / inhibitory molecule family, which currently includes 10 molecules: CD80 (B7.1), CD86 (B7.2), B7H1 (PD-L1 / CD274), B7-DC (PD-L2 / CD273), B7H2 (ICOSL), B7H3 (CD276), B7H4 (B7S1 / B7x / Vtcn1), B7H5 (VISTA), B7H6, and B7-H7 (HHLA2). Several members of the B7 family or their receptors, such as PD-L1 / PD1, CTLA4, B7H4, and VISTA, have been shown to be immune checkpoints.

[0006] B7-H7 is currently the newest B7 family molecule, and unlike other molecules in the family, it has three extracellular Ig domains. The in vitro function of B7-H7 has been subject to some controversy, which may be related to the different receptors it acts on. One of these receptors is CD28H, and it has been reported that B7-H7 can act on CD28H to promote the function of T cells or NK cells (Nat Commun. 2013; 4: 2043; Cancer Immunol Res. 2019; 7 (6): 939-951.), and another report has shown that B7-H7 can inhibit the function of T cells by acting on KIR3DL3 (Cancer Immunol Res. 2020 Nov 23; canimm. 0315. 2020.).

[0007] In normal tissues, B7-H7 is highly expressed mainly in tissues such as the gastrointestinal tract and bile duct. Patient sample studies have found that B7-H7 molecules are highly expressed in many tumor types, including breast cancer, lung cancer, intestinal cancer, and pancreatic cancer, and that the expression level tends to be negatively correlated with prognosis and survival rate (Clin Cancer Res. 2015 May 15; 21 (10): 2359-2366; Onco Targets Ther. 2018; 11: 1563-1570). Therefore, in the body, B7-H7 functions as an immune checkpoint and inhibits the immune response. Blocking the action of B7-H7 by producing neutralizing antibodies and reactivating the immune system is a promising therapeutic approach for B7-H7-high expressing tumors.

[0008] Currently, there are few studies on B7-H7, or all of them are in preclinical development, so there is a strong demand for the development of human-derived anti-B7-H7 antibodies that have high affinity, high biological activity, and high in vivo antitumor activity. Summary of the Invention

[0009] The technical problem to be solved by the present invention is to provide an anti-B7-H7 antibody or an antigen-binding fragment thereof, as well as a preparation method and application thereof, in order to overcome the shortcomings of anti-B7-H7 antibodies in the prior art.

[0010] In order to solve the above technical problem, a first aspect of the present invention provides an anti-B7-H7 antibody or an antigen-binding fragment thereof, the anti-B7-H7 antibody or the antigen-binding fragment thereof comprising a light chain variable region (VL) and / or a heavy chain variable region (VH), wherein: The VL comprises a complementarity determining region (CDR) of LCDR1 shown in the amino acid sequence of SEQ ID NO: 82, an LCDR2 shown in any one of the amino acid sequences of SEQ ID NO: 94 to 100, and / or an LCDR3 shown in any one of the amino acid sequences of SEQ ID NO: 111, 112, 114 to 116, 120, and 121, or a mutation thereof; The VH comprises a CDR or a mutation thereof, which is an HCDR1 represented by the amino acid sequence of SEQ ID NO: 7, an HCDR2 represented by the amino acid sequence of SEQ ID NO: 34 or 36, and / or an HCDR3 represented by any one of the amino acid sequences of SEQ ID NO: 57 to 68; Here, the mutation comprises an insertion, deletion or substitution of 3, 2 or 1 amino acids in the amino acid sequence of the CDR.

[0011] In the present application, "amino acid mutation" in the similar phrase "having 3, 2 or 1 amino acid insertion, deletion or substitution" refers to the presence of amino acid mutation in the sequence of the variant compared to the original amino acid sequence, including the original amino acid sequence in which an amino acid insertion, deletion or substitution has occurred. As an exemplary interpretation, the mutation to the CDR may include 3, 2 or 1 amino acid mutation, and these CDRs may be optionally mutated with the same or different number of amino acid residues selected, for example, one amino acid may be mutated in CDR1, and no amino acids in CDR2 and CDR3 may be mutated.

[0012] In the present application, the mutation may include mutations currently known to those skilled in the art. For example, some mutations may be made to an antibody during the process of producing or using the antibody, for example, mutations may be made to potential post-translational modifications (PTMs) sites, particularly in the CDR region, that may exist, including mutations related to antibody aggregation, deamidation-sensitive sites (NG, NS, NH, etc.), aspartic acid isomerism (DG, DP)-sensitive sites, N-glycosylation (N-{P}S / T)-sensitive sites, and oxidation-sensitive sites.

[0013] Preferably, the LCDR1 mutation comprises three, two or one amino acid substitutions of S5G, I6V / F, S7N, S8N / Y, W9N / Y and L10F in the amino acid sequence shown in SEQ ID NO:82, and the mutated amino acid sequence of LCDR1 is preferably as shown in any one of SEQ ID NOs:81, 83 to 88.

[0014] Preferably, the LCDR3 mutation has one amino acid substitution of N4Q, S5A and Y8V in the amino acid sequence shown in SEQ ID NO:112, or the LCDR3 mutation has two or one amino acid substitutions of Q1H, N4Y, N5I / K and L8Y in the amino acid sequence shown in SEQ ID NO:115, or the LCDR3 mutation has one amino acid substitution of N4Q and S5A in the amino acid sequence shown in SEQ ID NO:116, and the amino acid sequence of the LCDR3 mutation is preferably as shown in any one of SEQ ID NOs:113, 117 to 119, 122 to 125.

[0015] Preferably, the HCDR1 mutation has two or one amino acid substitutions of F2G and D6R / N / S / Y / T in the amino acid sequence shown in SEQ ID NO:7, and the amino acid sequence of the HCDR1 mutation is preferably as shown in any one of SEQ ID NOs:8 to 13.

[0016] Preferably, the HCDR2 mutation has two or one amino acid substitutions of Y2F, D3N / E, G4E / A, S5N / T / R and N6E / D / K in the amino acid sequence shown in SEQ ID NO:36, and the amino acid sequence of the HCDR2 mutation is preferably as shown in any one of SEQ ID NOs:27 to 33, 35, 37 to 40.

[0017] The S5G mentioned above generally refers to a mutation of the amino acid S at position 5 of the amino acid sequence shown in SEQ ID NO:82 to G, and other amino acid substitutions, such as I6V / F, S7N, S8N / Y, W9N / Y and L10F, are similar and their meanings will be understood by those skilled in the art.

[0018] Preferably, the amino acid sequence of the LCDR1 is as set forth in SEQ ID NO:87, the amino acid sequence of the LCDR2 is as set forth in SEQ ID NO:97, and the amino acid sequence of the LCDR3 is as set forth in SEQ ID NO:120; or the amino acid sequence of the LCDR1 is as set forth in SEQ ID NO:82, the amino acid sequence of the LCDR2 is as set forth in SEQ ID NO:94, and the amino acid sequence of the LCDR3 is as set forth in SEQ ID NO:112; or the amino acid sequence of the LCDR1 is as set forth in SEQ ID NO:82, the amino acid sequence of the LCDR2 is as set forth in SEQ ID NO:94, and the amino acid sequence of the LCDR3 is as set forth in SEQ ID NO:122; or the amino acid sequence of the LCDR1 is as set forth in SEQ ID NO:82 and the amino acid sequence of the LCDR2 is as set forth in SEQ ID NO: or the amino acid sequence of LCDR1 is as set forth in SEQ ID NO:85, the amino acid sequence of LCDR2 is as set forth in SEQ ID NO:97, and the amino acid sequence of LCDR3 is as set forth in SEQ ID NO:116; or the amino acid sequence of LCDR1 is as set forth in SEQ ID NO:85, the amino acid sequence of LCDR2 is as set forth in SEQ ID NO:97, and the amino acid sequence of LCDR3 is as set forth in SEQ ID NO:124; or the amino acid sequence of LCDR1 is as set forth in SEQ ID NO:85, the amino acid sequence of LCDR2 is as set forth in SEQ ID NO:97, and the amino acid sequence of LCDR3 is as set forth in SEQ ID NO:125; or the amino acid sequence of LCDR1 is as set forth in SEQ ID NO:85, the amino acid sequence of LCDR2 is as set forth in SEQ ID NO:97, and the amino acid sequence of LCDR3 is as set forth in SEQ ID NO:125. the amino acid sequence of said LCDR2 is as set forth in SEQ ID NO:94 and the amino acid sequence of said LCDR3 is as set forth in SEQ ID NO:111; or the amino acid sequence of said LCDR1 is as set forth in SEQ ID NO:the amino acid sequence of LCDR1 is as shown in SEQ ID NO:82, the amino acid sequence of LCDR2 is as shown in SEQ ID NO:94, and the amino acid sequence of LCDR3 is as shown in SEQ ID NO:111; or the amino acid sequence of LCDR1 is as shown in SEQ ID NO:82, the amino acid sequence of LCDR2 is as shown in SEQ ID NO:94, and the amino acid sequence of LCDR3 is as shown in SEQ ID NO:117; or the amino acid sequence of LCDR1 is as shown in SEQ ID NO:82, the amino acid sequence of LCDR2 is as shown in SEQ ID NO:96, and the amino acid sequence of LCDR3 is as shown in SEQ ID NO:114; or the amino acid sequence of LCDR1 is as shown in SEQ ID NO:83, the amino acid sequence of LCDR2 is as shown in SEQ ID NO:95, and the amino acid sequence of LCDR3 is as shown in SEQ ID NO: or the amino acid sequence of LCDR1 is as set forth in SEQ ID NO:83, the amino acid sequence of LCDR2 is as set forth in SEQ ID NO:98, and the amino acid sequence of LCDR3 is as set forth in SEQ ID NO:113; or the amino acid sequence of LCDR1 is as set forth in SEQ ID NO:83, the amino acid sequence of LCDR2 is as set forth in SEQ ID NO:99, and the amino acid sequence of LCDR3 is as set forth in SEQ ID NO:119; or the amino acid sequence of LCDR1 is as set forth in SEQ ID NO:84, the amino acid sequence of LCDR2 is as set forth in SEQ ID NO:95, and the amino acid sequence of LCDR3 is as set forth in SEQ ID NO:115; or the amino acid sequence of LCDR1 is as set forth in SEQ ID NO:86 and the amino acid sequence of LCDR2 is as set forth in SEQ ID NO: and the amino acid sequence of said LCDR3 is as set forth in SEQ ID NO:118; or the amino acid sequence of said LCDR1 is as set forth in SEQ ID NO:88 and the amino acid sequence of said LCDR2 is as set forth in SEQ ID NO:95.NO:100, and the amino acid sequence of said LCDR3 is as shown in SEQ ID NO:121.

[0019] Preferably, the amino acid sequence of HCDR1 is as set forth in SEQ ID NO:12, the amino acid sequence of HCDR2 is as set forth in SEQ ID NO:34, and the amino acid sequence of HCDR3 is as set forth in SEQ ID NO:66; or the amino acid sequence of HCDR1 is as set forth in SEQ ID NO:7, the amino acid sequence of HCDR2 is as set forth in SEQ ID NO:28, and the amino acid sequence of HCDR3 is as set forth in SEQ ID NO:58; or the amino acid sequence of HCDR1 is as set forth in SEQ ID NO:7, the amino acid sequence of HCDR2 is as set forth in SEQ ID NO:37, and the amino acid sequence of HCDR3 is as set forth in SEQ ID NO:58; or the amino acid sequence of HCDR1 is as set forth in SEQ ID NO:7, the amino acid sequence of HCDR2 is as set forth in SEQ ID NO:38, and the amino acid sequence of HCDR3 is as set forth in SEQ ID NO: or the amino acid sequence of HCDR1 is as shown in SEQ ID NO:9, the amino acid sequence of HCDR2 is as shown in SEQ ID NO:27, and the amino acid sequence of HCDR3 is as shown in SEQ ID NO:63; or the amino acid sequence of HCDR1 is as shown in SEQ ID NO:9, the amino acid sequence of HCDR2 is as shown in SEQ ID NO:39, and the amino acid sequence of HCDR3 is as shown in SEQ ID NO:63; or the amino acid sequence of HCDR1 is as shown in SEQ ID NO:9, the amino acid sequence of HCDR2 is as shown in SEQ ID NO:40, and the amino acid sequence of HCDR3 is as shown in SEQ ID NO:63; or the amino acid sequence of HCDR1 is as shown in SEQ ID NO:7, and the amino acid sequence of HCDR2 is as shown in SEQ ID NO: and the amino acid sequence of said HCDR3 is as set forth in SEQ ID NO:57, or the amino acid sequence of said HCDR1 is as set forth in SEQ ID NO:or the amino acid sequence of HCDR1 is as shown in SEQ ID NO:7, the amino acid sequence of HCDR2 is as shown in SEQ ID NO:28, and the amino acid sequence of HCDR3 is as shown in SEQ ID NO:59; or the amino acid sequence of HCDR1 is as shown in SEQ ID NO:7, the amino acid sequence of HCDR2 is as shown in SEQ ID NO:36, and the amino acid sequence of HCDR3 is as shown in SEQ ID NO:68; or the amino acid sequence of HCDR1 is as shown in SEQ ID NO:8, the amino acid sequence of HCDR2 is as shown in SEQ ID NO:29, and the amino acid sequence of HCDR3 is as shown in SEQ ID NO:60; or the amino acid sequence of HCDR1 is as shown in SEQ ID NO:8, the amino acid sequence of HCDR2 is as shown in SEQ ID NO:30, and the amino acid sequence of HCDR3 is as shown in SEQ ID NO: or the amino acid sequence of HCDR1 is as set forth in SEQ ID NO:8, the amino acid sequence of HCDR2 is as set forth in SEQ ID NO:32, and the amino acid sequence of HCDR3 is as set forth in SEQ ID NO:62; or the amino acid sequence of HCDR1 is as set forth in SEQ ID NO:9, the amino acid sequence of HCDR2 is as set forth in SEQ ID NO:27, and the amino acid sequence of HCDR3 is as set forth in SEQ ID NO:61; or the amino acid sequence of HCDR1 is as set forth in SEQ ID NO:9, the amino acid sequence of HCDR2 is as set forth in SEQ ID NO:31, and the amino acid sequence of HCDR3 is as set forth in SEQ ID NO:64; or the amino acid sequence of HCDR1 is as set forth in SEQ ID NO:10 and the amino acid sequence of HCDR2 is as set forth in SEQ ID NO: The amino acid sequence of the HCDR1 is as set forth in SEQ ID NO:11 and the amino acid sequence of the HCDR2 is as set forth in SEQ ID NO:29 and the amino acid sequence of the HCDR3 is as set forth in SEQ ID NO:62, or the amino acid sequence of the HCDR1 is as set forth in SEQ ID NO:11 and the amino acid sequence of the HCDR2 is as set forth in SEQ ID NO:11.the amino acid sequence of HCDR1 is as set forth in SEQ ID NO: 13, the amino acid sequence of HCDR2 is as set forth in SEQ ID NO: 35, and the amino acid sequence of HCDR3 is as set forth in SEQ ID NO: 67; In a preferred embodiment, in the anti-B7-H7 antibody or antigen-binding fragment thereof, the amino acid sequences of LCDR1, LCDR2 and LCDR3 contained in the VL are as shown in SEQ ID NOs:87, 97 and 120, respectively, and the amino acid sequences of HCDR1, HCDR2 and HCDR3 contained in the VH are as shown in SEQ ID NOs:12, 34 and 66, respectively.

[0020] In a preferred embodiment, in the anti-B7-H7 antibody or antigen-binding fragment thereof, the amino acid sequences of LCDR1, LCDR2 and LCDR3 contained in the VL are as shown in SEQ ID NOs:82, 94 and 112, respectively, and the amino acid sequences of HCDR1, HCDR2 and HCDR3 contained in the VH are as shown in SEQ ID NOs:7, 28 and 58, respectively.

[0021] In a preferred embodiment, in the anti-B7-H7 antibody or antigen-binding fragment thereof, the amino acid sequences of LCDR1, LCDR2 and LCDR3 contained in the VL are as shown in SEQ ID NOs:82, 94 and 112, respectively, and the amino acid sequences of HCDR1, HCDR2 and HCDR3 contained in the VH are as shown in SEQ ID NOs:7, 37 and 58, respectively.

[0022] In a preferred embodiment, in the anti-B7-H7 antibody or antigen-binding fragment thereof, the amino acid sequences of LCDR1, LCDR2 and LCDR3 contained in the VL are as shown in SEQ ID NOs:82, 94 and 122, respectively, and the amino acid sequences of HCDR1, HCDR2 and HCDR3 contained in the VH are as shown in SEQ ID NOs:7, 37 and 58, respectively.

[0023] In a preferred embodiment, in the anti-B7-H7 antibody or antigen-binding fragment thereof, the amino acid sequences of LCDR1, LCDR2 and LCDR3 contained in the VL are as shown in SEQ ID NOs:82, 94 and 123, respectively, and the amino acid sequences of HCDR1, HCDR2 and HCDR3 contained in the VH are as shown in SEQ ID NOs:7, 37 and 58, respectively.

[0024] In a preferred embodiment, in the anti-B7-H7 antibody or antigen-binding fragment thereof, the amino acid sequences of LCDR1, LCDR2 and LCDR3 contained in the VL are as shown in SEQ ID NOs:82, 94 and 112, respectively, and the amino acid sequences of HCDR1, HCDR2 and HCDR3 contained in the VH are as shown in SEQ ID NOs:7, 38 and 58, respectively.

[0025] In a preferred embodiment, in the anti-B7-H7 antibody or antigen-binding fragment thereof, the amino acid sequences of LCDR1, LCDR2 and LCDR3 contained in the VL are as shown in SEQ ID NOs:82, 94 and 122, respectively, and the amino acid sequences of HCDR1, HCDR2 and HCDR3 contained in the VH are as shown in SEQ ID NOs:7, 38 and 58, respectively.

[0026] In a preferred embodiment, in the anti-B7-H7 antibody or antigen-binding fragment thereof, the amino acid sequences of LCDR1, LCDR2 and LCDR3 contained in the VL are as shown in SEQ ID NOs:82, 94 and 123, respectively, and the amino acid sequences of HCDR1, HCDR2 and HCDR3 contained in the VH are as shown in SEQ ID NOs:7, 38 and 58, respectively.

[0027] In a preferred embodiment, in the anti-B7-H7 antibody or antigen-binding fragment thereof, the amino acid sequences of LCDR1, LCDR2 and LCDR3 contained in the VL are as shown in SEQ ID NOs:82, 94 and 122, respectively, and the amino acid sequences of HCDR1, HCDR2 and HCDR3 contained in the VH are as shown in SEQ ID NOs:7, 28 and 58, respectively.

[0028] In a preferred embodiment, in the anti-B7-H7 antibody or antigen-binding fragment thereof, the amino acid sequences of LCDR1, LCDR2 and LCDR3 contained in the VL are as shown in SEQ ID NOs:82, 94 and 123, respectively, and the amino acid sequences of HCDR1, HCDR2 and HCDR3 contained in the VH are as shown in SEQ ID NOs:7, 28 and 58, respectively.

[0029] In a preferred embodiment, in the anti-B7-H7 antibody or antigen-binding fragment thereof, the amino acid sequences of LCDR1, LCDR2 and LCDR3 contained in the VL are as shown in SEQ ID NOs:85, 97 and 116, respectively, and the amino acid sequences of HCDR1, HCDR2 and HCDR3 contained in the VH are as shown in SEQ ID NOs:9, 27 and 63, respectively.

[0030] In a preferred embodiment, in the anti-B7-H7 antibody or antigen-binding fragment thereof, the amino acid sequences of LCDR1, LCDR2 and LCDR3 contained in the VL are as shown in SEQ ID NOs:85, 97 and 116, respectively, and the amino acid sequences of HCDR1, HCDR2 and HCDR3 contained in the VH are as shown in SEQ ID NOs:9, 39 and 63, respectively.

[0031] In a preferred embodiment, in the anti-B7-H7 antibody or antigen-binding fragment thereof, the amino acid sequences of LCDR1, LCDR2 and LCDR3 contained in the VL are as shown in SEQ ID NOs:85, 97 and 124, respectively, and the amino acid sequences of HCDR1, HCDR2 and HCDR3 contained in the VH are as shown in SEQ ID NOs:9, 39 and 63, respectively.

[0032] In a preferred embodiment, in the anti-B7-H7 antibody or antigen-binding fragment thereof, the amino acid sequences of LCDR1, LCDR2 and LCDR3 contained in the VL are as shown in SEQ ID NOs:85, 97 and 125, respectively, and the amino acid sequences of HCDR1, HCDR2 and HCDR3 contained in the VH are as shown in SEQ ID NOs:9, 39 and 63, respectively.

[0033] In a preferred embodiment, in the anti-B7-H7 antibody or antigen-binding fragment thereof, the amino acid sequences of LCDR1, LCDR2 and LCDR3 contained in the VL are as shown in SEQ ID NOs:85, 97 and 116, respectively, and the amino acid sequences of HCDR1, HCDR2 and HCDR3 contained in the VH are as shown in SEQ ID NOs:9, 40 and 63, respectively.

[0034] In a preferred embodiment, in the anti-B7-H7 antibody or antigen-binding fragment thereof, the amino acid sequences of LCDR1, LCDR2 and LCDR3 contained in the VL are as shown in SEQ ID NOs:85, 97 and 124, respectively, and the amino acid sequences of HCDR1, HCDR2 and HCDR3 contained in the VH are as shown in SEQ ID NOs:9, 40 and 63, respectively.

[0035] In a preferred embodiment, in the anti-B7-H7 antibody or antigen-binding fragment thereof, the amino acid sequences of LCDR1, LCDR2 and LCDR3 contained in the VL are as shown in SEQ ID NOs:85, 97 and 125, respectively, and the amino acid sequences of HCDR1, HCDR2 and HCDR3 contained in the VH are as shown in SEQ ID NOs:9, 40 and 63, respectively.

[0036] In a preferred embodiment, in the anti-B7-H7 antibody or antigen-binding fragment thereof, the amino acid sequences of LCDR1, LCDR2 and LCDR3 contained in the VL are as shown in SEQ ID NOs:85, 97 and 124, respectively, and the amino acid sequences of HCDR1, HCDR2 and HCDR3 contained in the VH are as shown in SEQ ID NOs:9, 27 and 63, respectively.

[0037] In a preferred embodiment, in the anti-B7-H7 antibody or antigen-binding fragment thereof, the amino acid sequences of LCDR1, LCDR2 and LCDR3 contained in the VL are as shown in SEQ ID NOs:85, 97 and 125, respectively, and the amino acid sequences of HCDR1, HCDR2 and HCDR3 contained in the VH are as shown in SEQ ID NOs:9, 27 and 63, respectively.

[0038] In a preferred embodiment, in the anti-B7-H7 antibody or antigen-binding fragment thereof, the amino acid sequences of LCDR1, LCDR2 and LCDR3 contained in the VL are as shown in SEQ ID NOs:81, 94 and 111, respectively, and the amino acid sequences of HCDR1, HCDR2 and HCDR3 contained in the VH are as shown in SEQ ID NOs:7, 27 and 57, respectively.

[0039] In a preferred embodiment, in the anti-B7-H7 antibody or antigen-binding fragment thereof, the amino acid sequences of LCDR1, LCDR2 and LCDR3 contained in the VL are as shown in SEQ ID NOs:82, 94 and 112, respectively, and the amino acid sequences of HCDR1, HCDR2 and HCDR3 contained in the VH are as shown in SEQ ID NOs:7, 28 and 59, respectively.

[0040] In a preferred embodiment, in the anti-B7-H7 antibody or antigen-binding fragment thereof, the amino acid sequences of LCDR1, LCDR2 and LCDR3 contained in the VL are as shown in SEQ ID NOs:83, 95 and 113, respectively, and the amino acid sequences of HCDR1, HCDR2 and HCDR3 contained in the VH are as shown in SEQ ID NOs:8, 29 and 60, respectively.

[0041] In a preferred embodiment, in the anti-B7-H7 antibody or antigen-binding fragment thereof, the amino acid sequences of LCDR1, LCDR2 and LCDR3 contained in the VL are as shown in SEQ ID NOs:82, 96 and 114, respectively, and the amino acid sequences of HCDR1, HCDR2 and HCDR3 contained in the VH are as shown in SEQ ID NOs:9, 27 and 61, respectively.

[0042] In a preferred embodiment, in the anti-B7-H7 antibody or antigen-binding fragment thereof, the amino acid sequences of LCDR1, LCDR2 and LCDR3 contained in the VL are as shown in SEQ ID NOs:84, 95 and 115, respectively, and the amino acid sequences of HCDR1, HCDR2 and HCDR3 contained in the VH are as shown in SEQ ID NOs:10, 29 and 62, respectively.

[0043] In a preferred embodiment, in the anti-B7-H7 antibody or antigen-binding fragment thereof, the amino acid sequences of LCDR1, LCDR2 and LCDR3 contained in the VL are as shown in SEQ ID NOs:83, 98 and 113, respectively, and the amino acid sequences of HCDR1, HCDR2 and HCDR3 contained in the VH are as shown in SEQ ID NOs:8, 30 and 62, respectively.

[0044] In a preferred embodiment, in the anti-B7-H7 antibody or antigen-binding fragment thereof, the amino acid sequences of LCDR1, LCDR2 and LCDR3 contained in the VL are as shown in SEQ ID NOs:82, 94 and 117, respectively, and the amino acid sequences of HCDR1, HCDR2 and HCDR3 contained in the VH are as shown in SEQ ID NOs:9, 31 and 64, respectively.

[0045] In a preferred embodiment, in the anti-B7-H7 antibody or antigen-binding fragment thereof, the amino acid sequences of LCDR1, LCDR2 and LCDR3 contained in the VL are as shown in SEQ ID NOs:86, 95 and 118, respectively, and the amino acid sequences of HCDR1, HCDR2 and HCDR3 contained in the VH are as shown in SEQ ID NOs:8, 32 and 62, respectively.

[0046] In a preferred embodiment, in the anti-B7-H7 antibody or antigen-binding fragment thereof, the amino acid sequences of LCDR1, LCDR2 and LCDR3 contained in the VL are as shown in SEQ ID NOs:83, 99 and 119, respectively, and the amino acid sequences of HCDR1, HCDR2 and HCDR3 contained in the VH are as shown in SEQ ID NOs:11, 33 and 65, respectively.

[0047] In a preferred embodiment, in the anti-B7-H7 antibody or antigen-binding fragment thereof, the amino acid sequences of LCDR1, LCDR2 and LCDR3 contained in the VL are as shown in SEQ ID NOs:88, 100 and 121, respectively, and the amino acid sequences of HCDR1, HCDR2 and HCDR3 contained in the VH are as shown in SEQ ID NOs:13, 35 and 67, respectively.

[0048] In a preferred embodiment, in the anti-B7-H7 antibody or antigen-binding fragment thereof, the amino acid sequences of LCDR1, LCDR2 and LCDR3 contained in the VL are as shown in SEQ ID NOs:82, 94 and 111, respectively, and the amino acid sequences of HCDR1, HCDR2 and HCDR3 contained in the VH are as shown in SEQ ID NOs:7, 36 and 68, respectively.

[0049] In the present invention, the amino acid sequences of the CDRs listed above are all shown according to the Chothia definition rules. However, as known to those skilled in the art, the CDRs of antibodies can be defined in various ways in the art, such as the Kabat definition rules based on sequence variability (see Kabat et al., Protein Sequence in Immunology, 5th Edition, National Institutes of Health, Bethesda, MD (1991)) and the Chothia definition rules based on the location of structural loop regions (see J Mol Biol 273:927-48, 1997). In the technical solution of the present invention, the amino acid residues in the variable domain sequence can also be determined using the Combined definition rules, which include the Kabat definition and the Chothia definition. Here, the Combined definition rules combine the scope of the Kabat definition and the Chothia definition to obtain a larger scope based on this, and the details thereof can be seen in Tables 1-6 in the Examples section. As will be appreciated by those skilled in the art, unless otherwise specified, the terms "CDR" and "complementarity determining region" of a given antibody or region thereof (e.g., variable region) should be understood to cover the complementarity determining regions defined by any one of the above known schemes described in the present invention. Although the scope claimed in the present invention is the sequence shown based on the Chothia definition rules, corresponding amino acid sequences based on other CDR definition rules also fall within the scope of protection of the present invention.

[0050] Preferably, the light chain variable region (VL) further comprises a light chain variable region framework region (VL FWR), the VL FWR being a light chain variable region framework region of a human antibody, and the gene encoding the VL FWR is preferably derived from germline V gene IGKV1-5*03, IGKV3-15*01, IGKV1-27*01 or IGKV1-9*01. More preferably, the VL FWR comprises a VL FWR1 having an amino acid sequence as set forth in any one of SEQ ID NOs:74-79 or a mutant thereof, a VL FWR2 having an amino acid sequence as set forth in any one of SEQ ID NOs:90-92 or a mutant thereof, a VL FWR3 having an amino acid sequence as set forth in any one of SEQ ID NOs:102-109 or a mutant thereof, and a VL FWR4 having an amino acid sequence as set forth in any one of SEQ ID NOs:127-130 or a mutant thereof. wherein said mutation comprises 3, 2 or 1 amino acid insertions, deletions, substitutions and duplications in the amino acid sequence of said VL FWR.

[0051] Preferably, the heavy chain variable region (VH) further comprises a heavy chain variable region framework region (VH FWR), the VH FWR being a heavy chain variable region framework region of a human antibody, and the gene encoding the VH FWR is preferably derived from a germline V gene IGHV3-33*01, IGHV3-33*06 or IGHV1-69*01. More preferably, the VH FWR comprises a VH FWR1 having an amino acid sequence as set forth in any one of SEQ ID NOs:2 to 5 or a mutant thereof, a VH FWR2 having an amino acid sequence as set forth in any one of SEQ ID NOs:15 to 25 or a mutant thereof, a VH FWR3 having an amino acid sequence as set forth in any one of SEQ ID NOs:42 to 55 or a mutant thereof, and a VH FWR4 having an amino acid sequence as set forth in any one of SEQ ID NOs:70 to 72 or a mutant thereof. wherein said mutation comprises 3, 2 or 1 amino acid insertion, deletion, substitution and duplication in the amino acid sequence of said VH FWR.

[0052] In one embodiment of the invention, the VL comprises an amino acid sequence as set forth in any one of SEQ ID NOs: 151-167 or a mutation thereof. In one embodiment of the invention, the VH comprises an amino acid sequence as set forth in any one of SEQ ID NOs: 132-149 or a mutation thereof.

[0053] In a preferred embodiment, the VL comprises the amino acid sequence set forth in SEQ ID NO:161 and the VH comprises the amino acid sequence set forth in SEQ ID NO:143. In a preferred embodiment, the VL comprises the amino acid sequence set forth in SEQ ID NO:152 and the VH comprises the amino acid sequence set forth in SEQ ID NO:133. In a preferred embodiment, the VL comprises the amino acid sequence set forth in SEQ ID NO:152 and the VH comprises the amino acid sequence set forth in SEQ ID NO:146. In a preferred embodiment, the VL comprises the amino acid sequence set forth in SEQ ID NO:164 and the VH comprises the amino acid sequence set forth in SEQ ID NO:146. In a preferred embodiment, the VL comprises the amino acid sequence set forth in SEQ ID NO:165 and the VH comprises the amino acid sequence set forth in SEQ ID NO:146. In a preferred embodiment, the VL comprises the amino acid sequence set forth in SEQ ID NO:152, and the VH comprises the amino acid sequence set forth in SEQ ID NO:147. In a preferred embodiment, the VL comprises the amino acid sequence set forth in SEQ ID NO:164, and the VH comprises the amino acid sequence set forth in SEQ ID NO:147. In a preferred embodiment, the VL comprises the amino acid sequence set forth in SEQ ID NO:165, and the VH comprises the amino acid sequence set forth in SEQ ID NO:147. In a preferred embodiment, the VL comprises the amino acid sequence set forth in SEQ ID NO:164, and the VH comprises the amino acid sequence set forth in SEQ ID NO:133. In a preferred embodiment, the VL comprises the amino acid sequence set forth in SEQ ID NO:165, and the VH comprises the amino acid sequence set forth in SEQ ID NO:133. In a preferred embodiment, the VL comprises the amino acid sequence set forth in SEQ ID NO:156, and the VH comprises the amino acid sequence set forth in SEQ ID NO:138.In a preferred embodiment, the VL comprises the amino acid sequence set forth in SEQ ID NO:156 and the VH comprises the amino acid sequence set forth in SEQ ID NO:148. In a preferred embodiment, the VL comprises the amino acid sequence set forth in SEQ ID NO:166 and the VH comprises the amino acid sequence set forth in SEQ ID NO:148. In a preferred embodiment, the VL comprises the amino acid sequence set forth in SEQ ID NO:167 and the VH comprises the amino acid sequence set forth in SEQ ID NO:148. In a preferred embodiment, the VL comprises the amino acid sequence set forth in SEQ ID NO:156 and the VH comprises the amino acid sequence set forth in SEQ ID NO:149. In a preferred embodiment, the VL comprises the amino acid sequence set forth in SEQ ID NO:166 and the VH comprises the amino acid sequence set forth in SEQ ID NO:149. In a preferred embodiment, the VL comprises the amino acid sequence set forth in SEQ ID NO:167 and the VH comprises the amino acid sequence set forth in SEQ ID NO:149. In a preferred embodiment, the VL comprises the amino acid sequence set forth in SEQ ID NO:166 and the VH comprises the amino acid sequence set forth in SEQ ID NO:138. In a preferred embodiment, the VL comprises the amino acid sequence set forth in SEQ ID NO:167 and the VH comprises the amino acid sequence set forth in SEQ ID NO:138. In a preferred embodiment, the VL comprises the amino acid sequence set forth in SEQ ID NO:151 and the VH comprises the amino acid sequence set forth in SEQ ID NO:132. In a preferred embodiment, the VL comprises the amino acid sequence set forth in SEQ ID NO:152 and the VH comprises the amino acid sequence set forth in SEQ ID NO:134. In a preferred embodiment, the VL comprises the amino acid sequence set forth in SEQ ID NO:153, and the VH comprises the amino acid sequence set forth in SEQ ID NO:135.In a preferred embodiment, the VL comprises the amino acid sequence set forth in SEQ ID NO:154 and the VH comprises the amino acid sequence set forth in SEQ ID NO:136. In a preferred embodiment, the VL comprises the amino acid sequence set forth in SEQ ID NO:155 and the VH comprises the amino acid sequence set forth in SEQ ID NO:137. In a preferred embodiment, the VL comprises the amino acid sequence set forth in SEQ ID NO:157 and the VH comprises the amino acid sequence set forth in SEQ ID NO:139. In a preferred embodiment, the VL comprises the amino acid sequence set forth in SEQ ID NO:158 and the VH comprises the amino acid sequence set forth in SEQ ID NO:140. In a preferred embodiment, the VL comprises the amino acid sequence set forth in SEQ ID NO:159 and the VH comprises the amino acid sequence set forth in SEQ ID NO:141. In a preferred embodiment, the VL comprises the amino acid sequence set forth in SEQ ID NO:160 and the VH comprises the amino acid sequence set forth in SEQ ID NO:142. In a preferred embodiment, the VL comprises the amino acid sequence set forth in SEQ ID NO:162 and the VH comprises the amino acid sequence set forth in SEQ ID NO:144. In a preferred embodiment, the VL comprises the amino acid sequence set forth in SEQ ID NO:163 and the VH comprises the amino acid sequence set forth in SEQ ID NO:145. The above mutations involve the deletion, substitution or addition of one or more amino acid residues in the amino acid sequence of the VH and / or VL, and the mutated amino acid sequence has at least 85% sequence identity with the amino acid sequence of the VH and / or VL and maintains or improves the binding of the antibody to B7-H7, wherein the at least 85% sequence identity is preferably at least 90% sequence identity, more preferably at least 95%, 96%, 97%, 98% sequence identity, and most preferably at least 99% sequence identity.

[0054] Preferably, the anti-B7-H7 antibody or antigen-binding fragment thereof according to the present invention may be a full-length antibody, a Fab, a Fab', a F(ab')2, an Fv, preferably an scFv, a bispecific antibody, a multispecific antibody, a heavy chain antibody or a single domain antibody, or a monoclonal or polyclonal antibody produced from said antibodies.

[0055] In the present application, the "Fab fragment" consists of one light chain and one heavy chain CH1 and variable region. The heavy chain of the Fab molecule cannot form disulfide bonds with another heavy chain molecule. The "Fc" region contains two heavy chain fragments including the CH1 and CH2 domains of the antibody. The two heavy chain fragments consist of two or more disulfide bonds and are held together by the hydrophobic effect of the CH3 domain. The "Fab fragment" contains one light chain and a portion of one heavy chain including the VH domain, the CH1 domain, and the region between the CH1 and CH2 domains, which allows the two heavy chains of the two Fab' fragments to form an interchain disulfide bond to form a F(ab')2 molecule. The "F(ab')2 fragment" contains two light chains and two heavy chains including a portion of the constant region between the CH1 and CH2 domains, which allows the two heavy chains to form an interchain disulfide bond to form a F(ab')2 molecule. Thus, an F(ab')2 fragment consists of two Fab' fragments held together via disulfide bonds between the two heavy chains. The term "Fv" refers to an antibody fragment consisting of the VL and VH domains of a single arm of an antibody, but lacks the constant region.

[0056] In the present application, the scFv (single chain antibody fragment) may be a conventional single chain antibody in the art, which comprises a heavy chain variable region, a light chain variable region and a short peptide of 15-20 amino acids, in which the VL and VH domains are paired to form a monovalent molecule via a linker that allows them to be produced as a single polypeptide chain [see, for example, Bird et al., Science 242:423-426 (1988) and Huston et al., Proc. Natl. Acad. Sci. USA 85:5879-5883 (1988)]. Such scFv molecules may have the general structure NH2-VL-linker-VH-COOH or NH2-VH-linker-VL-COOH. A suitable prior art linker consists of an overlapping G4S amino acid sequence or a variant thereof. For example, a linker having the amino acid sequence (G4S)4 or (G4S)3 may be used, although variants thereof may also be used.

[0057] In this application, the term "multispecific antibodies" is used in its broadest sense to cover antibodies with specificity for multiple epitopes. These multispecific antibodies include, but are not limited to, antibodies comprising a heavy chain variable region (VH) and a light chain variable region (VL), where the VH-VL unit has specificity for multiple epitopes, antibodies with two or more VL and VH regions, where each VH-VL unit binds to a different target or a different epitope on the same target, antibodies with two or more single variable regions, where each single variable region binds to a different target or a different epitope on the same target, full length antibodies, antibody fragments, diabodies, and triabodies, antibody fragments that are covalently or non-covalently linked together, etc.

[0058] In this application, the term monoclonal antibody or mAb or Ab refers to an antibody obtained from a single clonal cell line, including but not limited to eukaryotic, prokaryotic or phage clonal cell lines.

[0059] In the present application, the above-mentioned "heavy chain antibody" refers to an antibody that contains only one heavy chain variable domain (VHH) and two common CH2 and CH3 domains, also called HCAbs.

[0060] "Single domain antibodies", also known as "nanobiodies", refer to VHH structures cloned from heavy chain antibodies and are the smallest known units capable of binding to a target antigen.

[0061] In one embodiment of the present invention, the anti-B7-H7 antibody or antigen-binding fragment thereof is a full-length antibody comprising an antibody heavy chain constant region and an antibody light chain constant region. Preferably, the heavy chain constant region is selected from hIgG1, hIgG2, hIgG3, or hIgG4, and the light chain constant region is selected from a κ chain or a λ chain of a human-derived antibody. More preferably, the heavy chain constant region is hIgG1, and the light chain constant region is a κ chain of a human-derived antibody.

[0062] In a preferred embodiment, the full length antibody comprises a heavy chain and a light chain, wherein the heavy chain comprises an amino acid sequence as set forth in any one of SEQ ID NOs:169-190 or a mutation thereof, and / or the light chain comprises an amino acid sequence as set forth in any one of SEQ ID NOs:192-208 or a mutation thereof.

[0063] In some preferred embodiments, the full length antibody comprises a heavy chain and a light chain, wherein the heavy chain comprises the amino acid sequence set forth in SEQ ID NO:186, and the light chain comprises the amino acid sequence set forth in SEQ ID NO:202. In some preferred embodiments, the full length antibody comprises a heavy chain and a light chain, wherein the heavy chain comprises the amino acid sequence set forth in SEQ ID NO:180, and the light chain comprises the amino acid sequence set forth in SEQ ID NO:202. In some preferred embodiments, the full length antibody comprises a heavy chain and a light chain, wherein the heavy chain comprises the amino acid sequence set forth in SEQ ID NO:184, and the light chain comprises the amino acid sequence set forth in SEQ ID NO:193. In some preferred embodiments, the full length antibody comprises a heavy chain and a light chain, wherein the heavy chain comprises the amino acid sequence set forth in SEQ ID NO:170, and the light chain comprises the amino acid sequence set forth in SEQ ID NO:193. In some preferred embodiments, the full length antibody comprises a heavy chain and a light chain, wherein the heavy chain comprises the amino acid sequence set forth in SEQ ID NO:187, and the light chain comprises the amino acid sequence set forth in SEQ ID NO:193. In some preferred embodiments, the full length antibody comprises a heavy chain and a light chain, wherein the heavy chain comprises the amino acid sequence set forth in SEQ ID NO:187, and the light chain comprises the amino acid sequence set forth in SEQ ID NO:205. In some preferred embodiments, the full length antibody comprises a heavy chain and a light chain, wherein the heavy chain comprises the amino acid sequence set forth in SEQ ID NO:187, and the light chain comprises the amino acid sequence set forth in SEQ ID NO:206. In some preferred embodiments, the full length antibody comprises a heavy chain and a light chain, wherein the heavy chain comprises the amino acid sequence set forth in SEQ ID NO:188, and the light chain comprises the amino acid sequence set forth in SEQ ID NO:193. In a preferred embodiment, the full length antibody comprises a heavy chain and a light chain, wherein the heavy chain comprises the amino acid sequence set forth in SEQ ID NO:188, and the light chain comprises the amino acid sequence set forth in SEQ ID NO:205.In some preferred embodiments, the full length antibody comprises a heavy chain and a light chain, wherein the heavy chain comprises the amino acid sequence set forth in SEQ ID NO:188, and the light chain comprises the amino acid sequence set forth in SEQ ID NO:206. In some preferred embodiments, the full length antibody comprises a heavy chain and a light chain, wherein the heavy chain comprises the amino acid sequence set forth in SEQ ID NO:184, and the light chain comprises the amino acid sequence set forth in SEQ ID NO:205. In some preferred embodiments, the full length antibody comprises a heavy chain and a light chain, wherein the heavy chain comprises the amino acid sequence set forth in SEQ ID NO:184, and the light chain comprises the amino acid sequence set forth in SEQ ID NO:206. In some preferred embodiments, the full length antibody comprises a heavy chain and a light chain, wherein the heavy chain comprises the amino acid sequence set forth in SEQ ID NO:185, and the light chain comprises the amino acid sequence set forth in SEQ ID NO:197. In some preferred embodiments, the full length antibody comprises a heavy chain and a light chain, wherein the heavy chain comprises the amino acid sequence set forth in SEQ ID NO:175, and the light chain comprises the amino acid sequence set forth in SEQ ID NO:197. In some preferred embodiments, the full length antibody comprises a heavy chain and a light chain, wherein the heavy chain comprises the amino acid sequence set forth in SEQ ID NO:189, and the light chain comprises the amino acid sequence set forth in SEQ ID NO:197. In some preferred embodiments, the full length antibody comprises a heavy chain and a light chain, wherein the heavy chain comprises the amino acid sequence set forth in SEQ ID NO:189, and the light chain comprises the amino acid sequence set forth in SEQ ID NO:207. In some preferred embodiments, the full length antibody comprises a heavy chain and a light chain, wherein the heavy chain comprises the amino acid sequence set forth in SEQ ID NO:189, and the light chain comprises the amino acid sequence set forth in SEQ ID NO:208. In a preferred embodiment, the full length antibody comprises a heavy chain and a light chain, wherein the heavy chain comprises the amino acid sequence set forth in SEQ ID NO:190, and the light chain comprises the amino acid sequence set forth in SEQ ID NO:197.In some preferred embodiments, the full length antibody comprises a heavy chain and a light chain, wherein the heavy chain comprises the amino acid sequence set forth in SEQ ID NO:190, and the light chain comprises the amino acid sequence set forth in SEQ ID NO:207. In some preferred embodiments, the full length antibody comprises a heavy chain and a light chain, wherein the heavy chain comprises the amino acid sequence set forth in SEQ ID NO:190, and the light chain comprises the amino acid sequence set forth in SEQ ID NO:208. In some preferred embodiments, the full length antibody comprises a heavy chain and a light chain, wherein the heavy chain comprises the amino acid sequence set forth in SEQ ID NO:185, and the light chain comprises the amino acid sequence set forth in SEQ ID NO:207. In some preferred embodiments, the full length antibody comprises a heavy chain and a light chain, wherein the heavy chain comprises the amino acid sequence set forth in SEQ ID NO:185, and the light chain comprises the amino acid sequence set forth in SEQ ID NO:208. In some preferred embodiments, the full length antibody comprises a heavy chain and a light chain, wherein the heavy chain comprises the amino acid sequence set forth in SEQ ID NO:169, and the light chain comprises the amino acid sequence set forth in SEQ ID NO:192. In some preferred embodiments, the full length antibody comprises a heavy chain and a light chain, wherein the heavy chain comprises the amino acid sequence set forth in SEQ ID NO:171, and the light chain comprises the amino acid sequence set forth in SEQ ID NO:193. In some preferred embodiments, the full length antibody comprises a heavy chain and a light chain, wherein the heavy chain comprises the amino acid sequence set forth in SEQ ID NO:172, and the light chain comprises the amino acid sequence set forth in SEQ ID NO:194. In some preferred embodiments, the full length antibody comprises a heavy chain and a light chain, wherein the heavy chain comprises the amino acid sequence set forth in SEQ ID NO:173, and the light chain comprises the amino acid sequence set forth in SEQ ID NO:195. In a preferred embodiment, the full length antibody comprises a heavy chain and a light chain, wherein the heavy chain comprises the amino acid sequence set forth in SEQ ID NO:174, and the light chain comprises the amino acid sequence set forth in SEQ ID NO:196.In some preferred embodiments, the full length antibody comprises a heavy chain and a light chain, wherein the heavy chain comprises the amino acid sequence set forth in SEQ ID NO:176, and the light chain comprises the amino acid sequence set forth in SEQ ID NO:198. In some preferred embodiments, the full length antibody comprises a heavy chain and a light chain, wherein the heavy chain comprises the amino acid sequence set forth in SEQ ID NO:177, and the light chain comprises the amino acid sequence set forth in SEQ ID NO:199. In some preferred embodiments, the full length antibody comprises a heavy chain and a light chain, wherein the heavy chain comprises the amino acid sequence set forth in SEQ ID NO:178, and the light chain comprises the amino acid sequence set forth in SEQ ID NO:200. In some preferred embodiments, the full length antibody comprises a heavy chain and a light chain, wherein the heavy chain comprises the amino acid sequence set forth in SEQ ID NO:179, and the light chain comprises the amino acid sequence set forth in SEQ ID NO:201. In a preferred embodiment, the full length antibody comprises a heavy chain and a light chain, wherein the heavy chain comprises the amino acid sequence set forth in SEQ ID NO:181 and the light chain comprises the amino acid sequence set forth in SEQ ID NO:203. In a preferred embodiment, the full length antibody comprises a heavy chain and a light chain, wherein the heavy chain comprises the amino acid sequence set forth in SEQ ID NO:182 and the light chain comprises the amino acid sequence set forth in SEQ ID NO:204. The mutations involve deletion, substitution or addition of one or more amino acid residues in the amino acid sequence of the heavy and / or light chain, and the mutated amino acid sequence has at least 85% sequence identity with the amino acid sequence of the heavy and / or light chain, and maintains or improves the binding of the antibody to B7-H7, wherein the at least 85% sequence identity is preferably at least 90% sequence identity, more preferably at least 95% sequence identity, and most preferably at least 99% sequence identity.

[0064] In order to solve the above technical problem, in a second aspect of the present invention, there is provided an isolated nucleic acid, wherein the nucleic acid encodes an anti-B7-H7 antibody or an antigen-binding fragment thereof described in the first aspect of the present invention.

[0065] The method for producing the nucleic acid is a conventional method in the art, and preferably includes a step of obtaining a nucleic acid molecule encoding the antibody by gene cloning technology, or a step of obtaining a nucleic acid molecule encoding the antibody by an artificial total sequence synthesis method. As known to those skilled in the art, substitution, deletion, modification, insertion or addition may be appropriately introduced into the base sequence of the amino acid sequence encoding the antibody to provide a polynucleotide homolog. In the present invention, a polynucleotide homolog can be produced by performing substitution, deletion or addition on one or more bases encoding the antibody sequence gene within a range that maintains the activity of the antibody.

[0066] In order to solve the above technical problem, in a third aspect of the present invention, there is provided a recombinant expression vector, which comprises the isolated nucleic acid according to the second aspect of the present invention.

[0067] Said recombinant expression vector can be obtained by a conventional method in the art, i.e., constructed by ligating the nucleic acid molecule described in the present application into various expression vectors. Said expression vectors can be various conventional vectors in the art, as long as they can accept the aforementioned nucleic acid molecule. Preferably, said expression vectors include eukaryotic expression vectors and / or prokaryotic expression vectors.

[0068] In order to solve the above technical problem, in a fourth aspect of the present invention, there is provided a transformant, the transformant comprising the recombinant expression vector according to the third aspect of the present invention.

[0069] The method for producing the transformant may be a conventional method in the art, for example, by transforming the recombinant expression vector into a host cell. The host cell of the transformant may be any of various conventional host cells in the art, as long as it can stably replicate the recombinant expression vector and effectively express the nucleic acid carried by the recombinant expression vector. Preferably, the host cell is a prokaryotic cell and / or a eukaryotic cell, and the prokaryotic cell is preferably an E. coli cell, such as TG1 or BL21 (expressing a single chain antibody or a Fab antibody), and the eukaryotic cell is preferably a HEK293 cell or a CHO cell (expressing a full-length IgG antibody). The preferred recombinant expression transformant of the present invention can be obtained by transforming the above-mentioned recombinant expression plasmid into a host cell. Here, the transformation method is a conventional transformation method in the art, and is preferably a chemical transformation method, a heat treatment method, or an electric conversion method.

[0070] In order to solve the above technical problems, in a fifth aspect of the present invention, there is provided a chimeric antigen receptor, which comprises the anti-B7-H7 antibody or an antigen-binding fragment thereof described in the first aspect of the present invention.

[0071] In order to solve the above technical problem, in a sixth aspect of the present invention, there is provided a genetically modified cell, said cell comprising a chimeric antigen receptor according to the fifth aspect of the present invention.

[0072] Preferably, said genetically modified cell is a eukaryotic cell, preferably an isolated human cell, more preferably an immune cell such as a T cell or a NK cell.

[0073] In order to solve the above technical problems, a seventh aspect of the present invention provides a method for producing an anti-B7-H7 antibody or an antigen-binding fragment thereof, the method comprising the steps of culturing the transformant described in the fourth aspect of the present invention and obtaining an anti-B7-H7 antibody or an antigen-binding fragment thereof from the culture.

[0074] In order to solve the above technical problems, in an eighth aspect of the present invention, there is provided an antibody-drug conjugate, comprising an antibody portion and a conjugate portion, wherein the antibody portion comprises the anti-B7-H7 antibody or antigen-binding fragment thereof according to the first aspect of the present invention, and the conjugate portion includes, but is not limited to, a detectable marker, a drug, a toxin, a cytokine, a radionuclide, an enzyme, or a combination thereof, and the antibody portion and the conjugate portion can be conjugated, for example, via a chemical bond or a linker.

[0075] In order to solve the above technical problems, in a ninth aspect of the present invention, there is provided a pharmaceutical composition, the pharmaceutical composition comprising an anti-B7-H7 antibody or an antigen-binding fragment thereof according to the first aspect of the present invention, a chimeric antigen receptor according to the fifth aspect of the present invention, a genetically modified cell according to the sixth aspect of the present invention and / or an antibody-drug conjugate according to the eighth aspect of the present invention.

[0076] The pharmaceutical composition of the present invention can be prepared in various dosage forms as required, and the beneficial dose can be determined and administered to the patient by the physician based on factors such as the type, age, weight, and general state of the disease of the patient, the mode of administration, etc. Preferably, the pharmaceutical composition is in the form of a liquid dosage form, a gas dosage form, a solid dosage form, or a semi-solid dosage form.

[0077] Preferably, the pharmaceutical composition may be administered orally, by injection, intranasally, transdermally or mucosally.

[0078] Preferably, the pharmaceutical composition further comprises another anti-tumor antibody as an active ingredient.

[0079] Preferably, the pharmaceutical composition further comprises a pharma- ceutical acceptable carrier. More preferably, the pharmaceutical composition comprises 0.01-99.99% of the anti-B7-H7 antibody or antigen-binding fragment thereof, the chimeric antigen receptor, the genetically modified cell, the antibody-drug conjugate, and 0.01-99.99% of the pharmaceutical carrier, the percentage being a mass percentage relative to the pharmaceutical composition.

[0080] The dosage level of the pharmaceutical composition according to the present invention can be adjusted depending on the amount of the composition to achieve the required diagnostic or therapeutic effect. The dosage regimen may be a single injection or multiple injections, or may be adjusted. The selected dose level and regimen are reasonably adjusted depending on various factors, including the activity and stability (half-life) of the pharmaceutical composition, the formulation, the route of administration, the combination with other drugs or treatments, the disease or condition to be detected and / or treated, and the health condition and treatment history of the subject to be treated.

[0081] The therapeutically effective dose of the pharmaceutical composition of the present invention can be initially estimated in cell culture experiments or animal models, such as rodents, rabbits, dogs, pigs and / or primates. Animal models can also be used to determine appropriate concentration ranges and routes of administration. These can then be used to determine effective doses and routes of administration to humans. In general, determining and adjusting effective amounts or doses to be administered, as well as evaluating when and how to make such adjustments, are known to those skilled in the art.

[0082] For further guidance regarding formulations, dosages, dosing schedules, and measurable therapeutic effects, see works such as Berkow et al. (2000) The Merck Manual of Medical Information and Merck & Co. Inc., Whitehouse Station, New Jersey; Ebadi (1998) CRC Desk Reference of Clinical Pharmacology.

[0083] As will be understood by those skilled in the art, the pharmaceutical composition may further include a combination therapeutic agent (i.e., used in the form of combination therapy), which includes, but is not limited to, chemotherapeutic agents, radiotherapeutic agents, immunosuppressants, cytotoxic drugs, etc. When performing combination therapy with a combination therapeutic agent, the above-mentioned antibody or antigen-binding fragment thereof, chimeric antigen receptor, genetically modified cell, antibody-drug conjugate, etc., and additional therapeutic or diagnostic agent may each be used as a single agent within any time range suitable for performing the intended treatment or diagnosis. Therefore, these single agents may be administered substantially simultaneously (i.e., as a single formulation or within a few minutes or hours) or sequentially in a specific order, depending on the actual needs of the specific application.

[0084] In order to solve the above technical problems, in a tenth aspect of the present invention, there is provided a kit comprising the antibody or antigen-binding fragment thereof according to the first aspect of the present invention, the chimeric antigen receptor according to the fifth aspect of the present invention, the genetically modified cell according to the sixth aspect of the present invention, the antibody-drug conjugate according to the eighth aspect of the present invention and / or the pharmaceutical composition according to the ninth aspect of the present invention.

[0085] Preferably, the kit further comprises (i) a device for administering the antibody or antigen-binding fragment thereof, or chimeric antigen receptor, or genetically modified cells, or antibody drug conjugate, or pharmaceutical composition, and / or (ii) instructions.

[0086] In order to solve the above technical problems, an eleventh aspect of the present invention provides an application of the antibody or antigen-binding fragment thereof according to the first aspect of the present invention, the chimeric antigen receptor according to the fifth aspect of the present invention, the genetically modified cell according to the sixth aspect of the present invention, the antibody-drug conjugate according to the eighth aspect of the present invention, the pharmaceutical composition according to the ninth aspect of the present invention and / or the kit according to the tenth aspect of the present invention in the manufacture of a drug for treating and / or preventing cancer.

[0087] Preferably, the cancer is selected from one or more of the group consisting of lung cancer, breast cancer, gastric cancer, small intestine cancer, colon cancer, rectal cancer, pancreatic cancer, renal cancer, bladder cancer, osteosarcoma, and the like.

[0088] In order to solve the above technical problems, in a 12th aspect of the present invention, there is provided an administration device, said administration device comprising the antibody or antigen-binding fragment thereof according to the first aspect of the present invention, the chimeric antigen receptor according to the fifth aspect of the present invention, the genetically modified cell according to the sixth aspect of the present invention, the antibody-drug conjugate according to the eighth aspect of the present invention, the pharmaceutical composition according to the ninth aspect of the present invention and / or the kit according to the tenth aspect of the present invention.

[0089] Preferably, the administration device further comprises a component for containing or administering to a subject the anti-B7-H7 antibody or antigen-binding fragment thereof, the chimeric antigen receptor, the genetically modified cell, the antibody drug conjugate, the pharmaceutical composition and / or the kit, e.g., a syringe, an injection device or an implantable administration device.

[0090] In order to solve the above technical problems, a thirteenth aspect of the present invention provides a method for detecting B7-H7, the method comprising the step of detecting using the antibody or antigen-binding fragment thereof according to the first aspect of the present invention, the chimeric antigen receptor according to the fifth aspect of the present invention, the genetically modified cell according to the sixth aspect of the present invention, the antibody-drug conjugate according to the eighth aspect of the present invention, the pharmaceutical composition according to the ninth aspect of the present invention and / or the kit according to the tenth aspect of the present invention.

[0091] Preferably, said detection is not for diagnostic and / or therapeutic purposes, such as the detection of B7-H7 in basic development.

[0092] In order to solve the above technical problems, the present invention further provides an application of the antibody or antigen-binding fragment thereof according to the first aspect of the present invention, the chimeric antigen receptor according to the fifth aspect of the present invention, the genetically modified cell according to the sixth aspect of the present invention, the antibody-drug conjugate according to the eighth aspect of the present invention, the pharmaceutical composition according to the ninth aspect of the present invention and / or the kit according to the tenth aspect of the present invention in the prevention and / or treatment of cancer. Preferably, the cancer is as described in the eleventh aspect of the present invention.

[0093] In order to solve the above technical problems, the present invention further provides a method for treating and / or preventing a B7-H7 related disease or condition (e.g. cancer, preferably a cancer according to the eleventh aspect of the present invention), the method comprising administering to a patient in need thereof a therapeutically effective amount of the antibody or antigen-binding fragment thereof according to the first aspect of the present invention, the chimeric antigen receptor according to the fifth aspect of the present invention, the genetically modified cell according to the sixth aspect of the present invention, the antibody drug conjugate according to the eighth aspect of the present invention, the pharmaceutical composition according to the ninth aspect of the present invention and / or the kit according to the tenth aspect of the present invention, thereby treating the patient in need thereof.

[0094] In this application, unless otherwise specified, scientific and technical terms used in this application have the meanings commonly understood by those skilled in the art. And the cell culture, molecular biology, nucleic acid chemistry, immunology laboratory operation steps used in this application are all common steps widely used in the corresponding fields. In addition, in order to better understand the present invention, the following provides the definitions and interpretations of related terms.

[0095] The three-letter and one-letter codes for amino acids used in this application are as known to those skilled in the art or as described in J. Biol. Chem, 243, p3558 (1968).

[0096] As used in this application, the terms "comprise" or "comprising" mean that the compositions and methods include the stated element, but do not exclude other elements, and, depending on the context, may also include "consisting of."

[0097] The term "antibody" as used herein may include immunoglobulins, which are tetrapeptide chain structures consisting of two identical heavy chains and two identical light chains linked via interchain disulfide bonds. The immunoglobulin heavy chain constant regions differ in amino acid composition and sequence, and therefore in their antigenicity. This allows immunoglobulins to be divided into five classes, or may be called immunoglobulin isotypes, namely IgM, IgD, IgG, IgA, and IgE, with the corresponding heavy chains being μ, δ, γ, α, and ε chains, respectively. Igs of the same class may be divided into various subclasses depending on the amino acid composition of their hinge regions and the number and position of the heavy chain disulfide bonds, for example, IgG may be divided into IgG1, IgG2, IgG3, and IgG4. The light chains are divided into κ or λ chains depending on the constant region. Each of the five classes of Igs may have either κ or λ chains.

[0098] In the present application, the antibody light chain variable region described in the present application may further comprise a light chain constant region, said light chain constant region comprising a kappa, lambda chain or a variant thereof of human origin.In the present application, the antibody heavy chain variable region described in the present application may further comprise a heavy chain constant region, said heavy chain constant region comprising an IgG1, 2, 3, 4 chain or a variant thereof of human origin.

[0099] In the light and heavy chains, the variable and constant regions are linked via a "J" region of about 12 or more amino acids, and the heavy chain further comprises a "D" region of about 3 or more amino acids. Each heavy chain consists of a heavy chain variable region (VH) and a heavy chain constant region (CH). The heavy chain constant region consists of three domains (CH1, CH2, and CH3). Each light chain consists of a light chain variable region (VL) and a light chain constant region (CL). The light chain constant region consists of one domain, CL. The constant region of an antibody can mediate the binding of immunoglobulins to host tissues or factors, including various cells of the immune system (e.g., effector cells) and the first component (C1q) of the classical complement system. Approximately 110 amino acids near the N-terminus of the antibody heavy and light chains are highly variable in sequence and are the variable region (V region), while the other amino acids near the C-terminus are relatively stable in sequence and are the constant region (C region). The variable region includes three hypervariable regions (HVRs) and four framework regions (FWRs) whose sequences are relatively conserved. The three hypervariable regions determine the specificity of the antibody and are also called complementarity determining regions (CDRs). Each light chain variable region (VL) and heavy chain variable region (VH) consists of three CDR regions and four FWR regions, which are arranged in the order of FWR1, CDR1, FWR2, CDR2, FWR3, CDR3, and FWR4 from the amino terminus to the carboxyl terminus. The three CDR regions of the light chain are referred to as VL CDR1, VL CDR2, and VL CDR3, and the three CDR regions of the heavy chain are referred to as VH CDR1, VH CDR2, and VH CDR3.

[0100] The term "human antibody" includes antibodies having variable and constant regions having human germline immunoglobulin sequences. Human antibodies of the present application may include amino acid residues not encoded by human germline immunoglobulin sequences (e.g., mutations introduced by random or site-specific induction in vitro or by somatic mutation in vivo). However, the term "human antibody" does not include antibodies in which CDR sequences derived from the germline of another mammalian species (e.g., mouse) have been grafted onto human framework sequences (i.e., "humanized antibodies").

[0101] As used in this application, the term "specificity" with respect to an antibody means an antibody that recognizes a specific antigen but does not substantially recognize or bind to other molecules in a sample. For example, an antibody that specifically binds to an antigen from one species can also bind to that antigen from one or more species. However, such species cross-reactivity does not in itself change the classification of the antibody based on its specificity. In another example, an antibody that specifically binds to an antigen can also bind to different allelic forms of the antigen. However, such cross-reactivity does not in itself change the classification of the antibody based on its specificity. In some cases, the term "specificity" or "specific binding" can be used to refer to the interaction of an antibody, protein, or peptide with a second chemical entity, meaning that the interaction is dependent on the presence of a specific structure (e.g., an antigenic determinant or epitope) in the chemical entity, e.g., an antibody generally recognizes and binds to a specific protein structure, but not to a protein. If an antibody is specific for epitope "A", in a reaction containing labeled "A" and an antibody, the presence of a molecule containing epitope A (or free unlabeled A) reduces the amount of labeled A that binds to the antibody.

[0102] In this application, the term "antigen-binding fragment" refers to antigen-binding fragments of antibodies and antibody analogs, which typically include at least a portion of the antigen-binding or variable regions (e.g., one or more CDRs) of a parental antibody. Antibody fragments retain at least some of the binding specificity of the parental antibody. Typically, when activity is expressed on a molar basis, antibody fragments retain at least 10% of the parental binding activity. Preferably, antibody fragments retain at least 50%, 60%, 70%, 80%, 90%, 95%, 99% or 100% or more of the parental antibody's binding affinity for the target. Examples of antigen-binding fragments include, but are not limited to, Fab, Fab', F(ab')2, Fv fragments, linear antibodies, single (heavy) chain antibodies, nanobodies, domain antibodies, and multispecific antibodies. Engineered antibody variants are reviewed in Holliger and Hudson (2005) Nat. Biotechnol. 23:1126-1136.

[0103] The term "chimeric antigen receptor" or "CAR" as used herein refers to an extracellular domain capable of binding to an antigen (extracellular binding domain), a hinge domain, a transmembrane domain (transmembrane region), and a polypeptide that transmits a cytoplasmic signal to the domain (i.e., an intracellular signal domain). The hinge domain may be considered to be a portion to provide flexibility to the extracellular antigen binding region. The intracellular signal domain generates a signal that can promote immune effector function of the cell of the CAR (e.g., CAR-T cell) through a defined signaling pathway, by a protein that generates a second messenger to transmit information intracellularly to regulate cellular activity, or by a protein that responds to such a messenger and functions as an effector. The intracellular signal domain includes a signaling domain and may further include a costimulatory intracellular domain from a costimulatory molecule.

[0104] "Identity", "mutation" refers to the sequence similarity between two polynucleotide sequences or between two polypeptides. If a position in two compared sequences is occupied by the same base or amino acid monomer subunit, for example, if each position in two DNA molecules is occupied by adenine, the molecules are homologous at that position. The percent identity between two sequences is a function of the number of matching or homologous positions shared by the two sequences divided by the number of positions compared x 100. For example, in optimal alignment of sequences, if 6 out of 10 positions in two sequences are matched or homologous, the two sequences are 60% homologous. Generally, alignment of two sequences is performed to obtain the maximum percent identity.

[0105] The terms "polypeptide", "peptide" and "protein" (when single chain) are used interchangeably in this application. The terms "nucleic acid", "nucleic acid sequence", "nucleotide sequence" or "polynucleotide sequence" and "polynucleotide" are used interchangeably.

[0106] The term "vector" refers to a nucleic acid delivery vehicle into which a polynucleotide can be inserted. If the vector allows for the expression of a protein encoded by the inserted polynucleotide, the vector is called an expression vector. A vector can be introduced into a host cell, such as by transformation, transduction or transfection, to allow the expression of the genetic material elements it carries in the host cell. Vectors are well known to those skilled in the art and include, but are not limited to, plasmids, phagemids, cosmids, artificial chromosomes, such as yeast artificial chromosomes (YACs), bacterial artificial chromosomes (BACs) or P1-derived artificial chromosomes (PACs), phages such as lambda or M13 phages, and animal viruses. Animal viruses that can be used as vectors include, but are not limited to, retroviruses (including lentiviruses), adenoviruses, adeno-associated viruses, herpes viruses (e.g., herpes simplex viruses), poxviruses, baculoviruses, papilloma viruses, papova viruses (SV40). A vector may contain multiple elements that control expression, including, but not limited to, promoter sequences, transcription initiation sequences, enhancer sequences, selection elements, and reporter genes. A vector may also contain an origin of replication.

[0107] As used in this application, the expressions "cell" and "cell line" are interchangeable and all such designations include the progeny thereof. The term "host cell" refers to a cell that can be used to introduce a vector, including, but not limited to, a prokaryotic cell such as E. coli, a fungal cell such as a yeast cell, or an animal cell such as a fibroblast cell, a CHO cell, a COS cell, an NSO cell, a HeLa cell, a BHK cell, a HEK 293 cell, or a human cell.

[0108] The term "transfection" refers to the introduction of exogenous nucleic acid into a eukaryotic cell. Transfection can be accomplished by a variety of means known in the art, including calcium phosphate-DNA co-precipitation, DEAE-dextran mediated transfection, polybrene mediated transfection, electroporation, microinjection, liposome fusion, lipofection, protoplast fusion, retroviral infection, and biolistics.

[0109] The term "immune cell" refers to a cell capable of eliciting an immune response, and "immune cell" and its other grammatical forms can refer to immune cells of any origin. "Immune cells" include, for example, leukocytes (white blood cells), lymphocytes (T cells, B cells, natural killer (NK) cells) derived from hematopoietic stem cells (HSCs) generated in the bone marrow, and cells derived from bone marrow (neutrophils, eosinophils, basophils, monocytes, macrophages, dendritic cells). The term "immune cell" can be human or non-human. For example, immune cells can be derived from blood, such as autologous T cells, allogeneic T cells, autologous NK cells, allogeneic NK cells, or from cell lines, such as NK cell lines obtained by EBV virus infection, NK cells induced and differentiated from embryonic stem cells and iPSCs, and the NK92 cell line.

[0110] As used herein, the term "T cells" refers to a class of lymphocytes that mature in the thymus. T cells play an important role in cell-mediated immunity and are distinct from other lymphocytes (e.g., B cells) by the presence of T cell receptors on the cell surface. "T cells" include all types of immune cells that express CD3, including T helper cells (CD4+ cells), cytotoxic T cells (CD8+ cells), natural killer T cells, T regulatory cells (Tregs), and gamma-delta T cells. "Cytotoxic cells" include CD8+ T cells, natural killer (NK) cells, and neutrophils, which can mediate cytotoxic responses. As used herein, the term "NK cells" refers to a class of lymphocytes that are derived from the bone marrow and play an important role in the innate immune system. NK cells provide a rapid immune response against virus-infected, tumor, or other stressed cells, even in the absence of antibodies and major histocompatibility complexes on the cell surface.

[0111] "Optional," "any one," "any" or "any one" means that the subsequently described event or circumstance may, but need not, occur, and the description includes cases where the event or circumstance has or has not occurred. For example, "optionally comprising an antibody heavy chain variable region" means that an antibody heavy chain variable region of a particular sequence may, but is not necessarily, present. As used herein, "a" and "a kind" refer to one or more of their grammatical objects. Unless the context clearly dictates otherwise, the term "or" means, and is used interchangeably with, "and / or" in the present invention. "About" and "approximately" are used to refer to the degree of error that may be present in a measured quantity, typically due to the nature or precision of the measurement. Exemplary degrees of error are typically within 10% of the amount, and more typically within 5%. The methods and compositions disclosed herein encompass polypeptides and nucleic acids having a given sequence, a variant sequence, or a substantially homologous or similar sequence thereto, for example, a sequence that is at least 85%, 90%, 95%, 99% or more identical to a given sequence. In the case of amino acid sequences, the term "substantially the same" is intended in the present invention to refer to a first amino acid sequence.

[0112] As used herein, the term "pharmaceutical composition" refers to a formulation in which the active ingredient is present in a form that allows the biological activity of the active ingredient to be effective and does not contain other ingredients that are unacceptably toxic to the subject to which the composition is administered. The composition is sterile.

[0113] As used in this application, the term "pharmacologically acceptable vector" refers to a carrier that is pharmacologically and / or physiologically compatible with the subject and the active ingredient, and is known in the art (see, e.g., Remington's Pharmaceutical Sciences. Edited by Gennaro AR, 19th ed. Pennsylvania: Mack Publishing Company, 1995), and includes, but is not limited to, pH adjusting agents, surfactants, adjuvants, ionic strength enhancing agents, diluents, agents that maintain osmolarity, agents that delay absorption, and preservatives. For example, pH adjusting agents include, but are not limited to, phosphate buffers. Surfactants include, but are not limited to, cationic, anionic, or nonionic surfactants, e.g., Tween-80. Ionic strength enhancing agents include, but are not limited to, sodium chloride. Preservatives include, but are not limited to, various antibacterial and antifungal agents, e.g., parabens, chlorobutanol, phenol, sorbic acid, and the like. Agents that maintain osmolarity include, but are not limited to, sugars, NaCl, and their analogs. Agents that delay absorption include, but are not limited to, monostearate and gelatin. Diluents include, but are not limited to, water, aqueous buffer solutions (e.g., buffered saline), ols and polyols (e.g., glycerol), and the like. Preservatives include, but are not limited to, various antibacterial and antifungal agents, such as, but not limited to, thimerosal, 2-phenoxyethanol, parabens, chlorobutanol, phenol, sorbic acid, and the like. Stabilizers have the meaning commonly understood by those skilled in the art and are capable of stabilizing the desired activity of the active ingredient in the pharmaceutical preparation, including, but not limited to, sodium glutamate, gelatin, SPGA, sugars (e.g., sorbitol, mannitol, starch, sucrose, lactose, dextran, or glucose), amino acids (e.g., glutamic acid, glycine), proteins (e.g., dried whey, albumin, or casein) or their degradation products (e.g., lactalbumin hydrolysate), and the like.

[0114] As used herein, EC 50The term refers to the concentration for 50% of maximal effect, i.e., the concentration capable of eliciting 50% of the maximal effect response.

[0115] As used herein, "cancer," "cancer" and "cancer patient" are intended to include all types of cancerous growths or neoplastic processes, metastatic tissues or malignantly transformed cells, tissues or organs, regardless of histopathological type or stage of invasiveness, examples of which include, but are not limited to, solid tumors, blood cancers, soft tissue tumors and metastatic lesions.

[0116] As can be understood by those skilled in the art, products comprising the anti-B7-H7 antibody or its antigen-binding fragment described in the present invention, such as CAR-T, TCR-T, diabody, multibody, ADC and other product forms, should fall within the protection scope of the present invention.

[0117] Each of the above preferred conditions can be arbitrarily combined in accordance with common knowledge in the art to obtain each of the preferred embodiments of the present invention.

[0118] All of the reagents and materials used in the present invention are commercially available.

[0119] The positive effect of the present invention is that the anti-B7-H7 antibody or antigen-binding fragment thereof described in the present invention has high affinity and high biological activity for B7-H7, which can effectively block the binding of B7-H7 protein to its receptor CD28H and the binding of B7-H7 protein to its receptor KIR3DL3, and the anti-B7-H7 antibody or antigen-binding fragment thereof specifically binds only to B7-H7 protein, does not cross-react with other member proteins of the B7 family, and has excellent stability. In addition, the anti-B7-H7 antibody or antigen-binding fragment thereof of the present invention also exhibits high in vivo anti-tumor activity. [Brief description of the drawings]

[0120] [Figure 1]FIG. 1 shows the results of binding of the B7-H7 primary antibody to the cell surface of human and cynomolgus monkey B7H7, and tumor cells HCC827. [Diagram 2] This figure shows the results of the B7-H7 LALA mutant antibody binding to tumor cells LS180. [Diagram 3] This figure shows the results of B7-H7 PTM mutant / LALA mutant antibody binding to tumor cell LS180. [Figure 4] FIG. 13 shows that B7-H7 antibody blocks the binding of B7-H7 protein to CD28H on the surface of HEK-293 cells. [Diagram 5] This figure shows the results that B7-H7 antibody and LALA mutant antibody block the binding of B7-H7 protein to KIR3DL3 on the CHO-K1 cell surface. [Figure 6] This figure shows the results that the B7-H7 antibody LALA mutant antibody blocks the binding of B7-H7 protein to KIR3DL3 protein. [Figure 7] FIG. 1 shows the results of the B7-H7 antibody activating T cells by blocking the immune inhibitory signal of B7-H7. [Figure 8] FIG. 1 shows the results that B7-H7 antibody does not act on B7-H7-negative cells and cannot activate T cells. [Figure 9] FIG. 1 shows the results of the B7-H7 antibody promoting target cell killing by NK cells. [Figure 10] FIG. 1 shows the results of cross-reactivity of anti-B7-H7 LALA mutant antibodies with other member proteins of the B7 family. [Figure 11] FIG. 1 shows serum stability results of anti-B7-H7 LALA mutant antibodies. [Figure 12] FIG. 1 shows the results of the antitumor effect of anti-B7-H7 antibody in a mouse tumor model. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0121] The present invention will be further described below by way of examples, but the present invention is not limited to the scope of the above examples. In the following examples, the experimental methods for which no specific conditions are specified are selected according to conventional methods and conditions or product instructions.

[0122] Example 1. Obtaining anti-B7-H7 antibody molecules B7-H7 recombinant protein is used to immunize laboratory animals to obtain antibody molecules that specifically bind to B7-H7, and the laboratory animals may be mice, rats, rabbits, sheep, camels, etc. Usually, the obtained antibody molecules are of non-human origin. After obtaining antibodies of non-human origin, it is necessary to carry out humanization operations on these molecules using antibody engineering techniques to reduce immunogenicity and increase drug discovery potential. However, the humanization process of antibodies is technically complex, and humanized molecules often have reduced affinity for antigens. Meanwhile, advances in transgenic technology have made it possible to generate genetically engineered mice that have a human immunoglobulin immune repertoire and delete their endogenous mouse immune repertoire. Harbour H2L2 mice (Harbour Antibodies BV) are transgenic mice with a human immunoglobulin immune repertoire, and antibodies produced from such transgenic mice have a fully human sequence and do not require further humanization operations.

[0123] Example 1.1. Mouse Immunization Harbour H2L2 mice were immunized multiple times with soluble recombinant human B7-H7-ECD-his fusion protein (Sino Biological, #16139-H08H) as the antigen. The antigen protein and the immune adjuvant were mixed to form an immunogen reagent, which was then injected subcutaneously into the groin or intraperitoneally. In each round of immunization, the total injection volume received by each mouse was 100 microliters. In the first immunization, each mouse was immunized with an immunogen reagent prepared by mixing 50 micrograms of antigen protein with complete Freund's adjuvant (Sigma, #F5881) in a 1:1 volume ratio. In each subsequent round of boosting, each mouse was immunized with an immunogen reagent prepared by mixing 25 micrograms of antigen protein with Sigma Adjuvant System adjuvant (Sigma, #S6322). The interval between each round of boosting was at least 2 weeks, and there were usually 4 to 5 rounds of boosting. The immunization times were days 0, 14, 28, 42, 56, 70, 84, and 96, and the antibody titers in the mouse serum were detected on days 49 and 77. Five days before the splenic B cell isolation of the H2L2 mice, the final booster was administered at a dose of 25 micrograms of antigen protein per mouse.

[0124] Example 1.2. Serum titer detection At specific time points, mouse serum was collected, and the titer of antibody binding to B7-H7 protein in the serum was detected by ELISA method, and the titer of antibody binding to B7-H7 overexpressing cells in the serum was detected by FACS method.

[0125] In the ELISA method, 100μL / well of ELISA plate (corning,9018) was coated with 1μg / mL hB7-H7-ECD-hFc protein (Sino Biological,# 16139-H02H), incubated overnight at 4℃, rinsed twice, blocked with 1% BSA in PBST at 37℃ for 2 hours, incubated with 100μL / well of serially diluted serum at 37℃ for 1 hour, rinsed three times, added with 100μL / well of anti-rat-HRP (sigma,# A5795) diluted 1:5000, and incubated at 37℃ for 30 minutes. After rinsing three times, TMB substrate was added at 100 μL / well, incubated for approximately 10 minutes, color development was stopped by adding 50 μL / well of 1N HCl, and absorbance was read at 450 nm (Molecular Devices, Plus 384).

[0126] In the FACS method, HEK293-B7-H7 cells were incubated with serially diluted mouse serum at 4°C for 1 hour, and the cells were washed twice, after which the secondary antibody anti rat IgG (H+L) (Life technologies, A11006) was added and incubated at 4°C for 1 hour, and after washing twice, the cells were resuspended and detected by flow cytometry (BD, Flibur). HEK293 cells were used as background control.

[0127] Example 1.3. Screening for anti-B7-H7 antibodies using hybridoma technology Mice with high serum titers were selected and sacrificed after one final immunization. Splenocytes and SP2 / 0 myeloma cells (ATCC, CRL-1581) were taken for electrofusion at a cell ratio of 4:1, and electrofusion parameters were V1:50V, t1:15s, V2:600V, t2:20μs, t3:0.5s, n:1, t4:7s, V+ / -:+, fade:on. The cells were resuspended in a culture medium of DMEM containing 20% ​​FBS and HT, and diluted to 1×10 5After 24 hours, 100μL / well of DMEM containing 20% ​​FBS and 2×HT was added and the cells were incubated. The supernatant was then taken to detect the antibody titer. Generally, 9-15 days after fusion, the supernatant was taken from the mice immunized with the protein and pre-screened with Acumen to detect the binding to HEK-293 / huB7-H7 cells. The positive clones were further confirmed by ELISA and FACS to detect the binding ability to HEK-293 cell line overexpressing human B7-H7 (HEK-293 / huB7-H7) and HEK-293 cell line overexpressing cynomolgus monkey B7-H7 (HEK-293 / cynoB7-H7). The positive wells were further subcloned by finite dilution method, and then further cloned by ELISA and FACS method. The clones that bound well to human and monkey B7-H7 were selected and sequenced.

[0128] Example 1.4. Sequence analysis and sequence optimization of anti-B7-H7 antibodies The nucleotide sequences encoding the variable domains of the antibody molecules and the corresponding amino acid sequences were obtained by conventional sequencing. Fourteen monoclonal sequences were obtained. In this example, the sequences of the variable domains of the anti-B7-H7 monoclonal antibody molecules obtained from immunized Harbour H2L2 mice are human-derived antibody sequences, and Table 1-1 lists their germline gene analysis and post-translational modification site (PTM) analysis.

[0129] After translational synthesis in cells, the amino acid chain of a protein or polypeptide may introduce chemical modifications called post-translational modifications (PTMs). In the case of antibodies, some PTM sites are very conserved; for example, the conserved amino acid asparagine Asn at position 297 (EU numbering) of the constant domain of human IgG1 antibodies is usually glycosylated to form a glycan, and the glycan structure is quite important for antibody structure and related effector functions. However, if PTMs are present in the variable domain of an antibody, particularly in the antigen-binding region (e.g., CDR), the presence of these PTMs may have a significant effect on antigen binding and may also change the physicochemical properties of the antibody. For example, glycosylation, deamidation, isomerization, oxidation, etc., may all increase the instability or heterogeneity of the antibody molecule, thereby increasing the difficulty and risk of antibody development. Therefore, avoiding some potential PTMs is very important for the development of therapeutic antibodies. With the accumulation of experience, it has been found that some PTMs are highly correlated with the composition of amino acid sequences, especially the "pattern" of the composition of adjacent amino acids, which allows the prediction of potential PTMs from the primary amino acid sequence of a protein. For example, the sequence pattern NxS / T (position 1 is asparagine, position 2 is any amino acid other than non-proline, and position 3 is serine or threonine) predicts N-linked glycosylation sites. The amino acid sequence pattern that causes PTMs may be derived from germline gene sequences, for example, the human germline gene fragment IGHV3-33, which naturally has the glycosylation pattern NST in the FR3 region, or may be derived from somatic hypermutation.

[0130] The formation of a particular PTM can be reduced or eliminated by disrupting the amino acid sequence pattern of the PTM by amino acid mutation. The method of designing the mutation varies depending on the antibody sequence and the PTM sequence pattern. One method is to replace the "hot spot" amino acid (e.g., N or S in the NS pattern) with an amino acid with similar physicochemical properties (e.g., mutate N to Q). If the PTM sequence pattern is derived from somatic hypermutation but does not exist in the germline gene sequence, another method is to replace the sequence pattern with the corresponding germline gene sequence. In practical operation, various mutation design methods can be used for the same PTM sequence pattern.

[0131] Table 1-2 lists new antibody molecule sequences obtained by performing amino acid mutations on the sequences of antibodies PR003249, PR003259 and PR003264, where PR003181 is a positive control and is from patent WO2014190356.

[0132] [Table 1]

[0133] [Table 2]

[0134] Example 1.5. Production of recombinant antibodies and characterization of their physicochemical properties Example 1.5.1. Antibody Expression and Purification This example introduces a general method for producing antibodies by mammalian host cells (e.g., human embryonic kidney cells HEK293 or Chinese hamster ovary cells CHO and cells derived therefrom), techniques such as transient transfection expression and affinity capture separation. This method is suitable for target antibodies that contain an Fc region, and the target antibodies may consist of one or more protein polypeptide chains or may be derived from one or more expression plasmids.

[0135] The amino acid sequence of the antibody polypeptide chain was converted to a nucleotide sequence by codon optimization method, and the encoded nucleotide sequence was synthesized and cloned into an expression vector compatible with the host cell. The plasmids encoding the antibody polypeptide chain were co-transfected into mammalian host cells in a specific ratio, and recombinant antibodies with correct folding and polypeptide chain assembly could be obtained using conventional recombinant protein expression and purification techniques. Specifically, FreeStyle™ 293-F cells (Thermo, #R79007) were cultured in FreeStyle™ F17 Expression Medium (Thermo, #A1383504). Before the transient transfection started, the cell concentration was adjusted to 6-8 × 10 5 The cells were adjusted to 1.2 × 10 cells / mL and cultured in a shaker at 37 °C and 8% CO2 for 24 hours until the cell concentration reached 1.2 × 10 6The ratio is cells / mL. 30 mL of cultured cells were prepared. Plasmids encoding antibody polypeptide chains were mixed in a certain ratio, and a total of 30 μg of plasmid (plasmid to cell ratio is 1 μg:1 mL) was dissolved in 1.5 mL of Opti-MEM serum-reduced medium (Thermo, #31985088), filtered through a 0.22 μm filter membrane, and sterilized. Next, 1.5 mL of Opti-MEM was taken, dissolved in 120 μL of 1 mg / mL PEI (Polysciences, #23966-2), and left to stand for 5 minutes. PEI was slowly added to the plasmid, incubated at room temperature for 10 minutes, and the plasmid-PEI mixed solution was slowly added dropwise while shaking the culture flask slowly, and cultured for 5 days in a shaker at 37 °C and 8% CO2. After 5 days, the cell viability was observed. The culture was collected, centrifuged at a rotation speed of 3300 g for 10 minutes, and the supernatant was taken, and the supernatant was centrifuged at high speed to remove impurities. A gravity column (Bio-Rad, #7311550) containing MabSelect™ (GE Healthcare, #71-5020-91) was equilibrated with PBS pH 7.4 buffer and washed with 2-5 column volumes. The supernatant sample was passed through the column, washed with 5-10 column volumes of PBS buffer, then the target protein was eluted with 0.1 M glycine at pH 3.5, then neutralized with Tris-HCl at pH 8.0, and finally concentrated with an ultrafiltration tube (Millipore, #UFC901024) and exchanged into PBS buffer or a buffer containing other components to obtain a purified recombinant antibody solution. Finally, the concentration was measured with a NanoDrop (Thermo, NanoDrop™ One), aliquoted, stored and waited.

[0136] Example 1.5.2. Protein Purity and Aggregation Analysis by SEC-HPLC In this example, analytical size exclusion chromatography (SEC) was used to analyze the purity and aggregate form of protein samples. An analytical chromatography column TSKgel G3000SWxl (Tosoh Bioscience, #08541, 5 μm, 7.8 mm × 30 cm) was connected to a high performance liquid chromatography HPLC (Agilent Technologies, Agilent 1260 Infinity II) and equilibrated with PBS buffer at room temperature for at least 1 hour. An appropriate amount of protein sample (at least 10 μg) was injected into the system after filtering with a 0.22 μm filter membrane, and the HPLC procedure was set up to pass the sample through the chromatography column at a flow rate of 1.0 mL / min with PBS buffer, with a maximum time of 25 minutes. The HPLC generated an analysis report and reported the retention times of components with different molecular sizes in the sample.

[0137] Example 1.5.3. Analysis of Protein Purity and Hydrophobicity by HIC-HPLC Analytical hydrophobic interaction chromatography (HIC) was used to analyze the purity and hydrophobicity of protein samples. An analytical chromatography column TSKge1 Buty1-NPR (Tosoh Bioscience, 14947, 4.6 mm × 3.5 cm) was connected to a high performance liquid chromatography HPLC (Agilent Technologies, Agilent 1260 Infinity II) and equilibrated with PBS buffer at room temperature for at least 1 h. The method was set to a 16-min linear gradient from 100% mobile phase A (20 mm histidine, 1.8 M ammonium sulfate, pH 6.0) to 100% mobile phase B (20 mm histidine, pH 6.0), with a flow rate of 0.7 mL / min, protein sample concentration of 1 mg / mL, sample injection volume of 20 μL, and detection wavelength of 280 nm. After collection, the chromatogram was integrated in the ChemStation software, the relevant data was calculated, and an analytical report was generated to report the retention times of components of different molecular sizes in the sample.

[0138] Example 1.5.4. Measurement of thermal stability of protein molecules by DSF Differential Scanning Fluorimetry (DSF) is a commonly used high-throughput method to measure the thermal stability of proteins. It reflects the process of protein denaturation by monitoring the change in the fluorescence intensity of the dye bound to the unfolded protein molecules using a real-time fluorescent quantitative PCR instrument, thereby reflecting the thermal stability of the protein molecules. This example uses the DSF method to measure the thermal denaturation temperature (Tm) of protein molecules. 10 μg of protein was added to a 96-well PCR plate (Thermo, #AB-0700 / W), then 2 μl 100× diluted dye SYPROTM (Invitrogen, #2008138) was added, and buffer was added to make the final volume 40 μl / well. The PCR plate was sealed and placed in a real-time fluorescent quantitative PCR instrument (Bio-Rad CFX96 PCR System), first incubated at 25°C for 5 min, then gradually increased in temperature from 25°C to 95°C with a gradient of 0.2°C / 0.2 min, and at the end of the experiment the temperature was reduced to 25°C. The data was analyzed and the Tm of the samples was calculated with Bio-Rad CFX Maestro software using the FRET scanning mode.

[0139] Example 1.6. Production of anti-B7-H7 fully human recombinant antibody The method described in Example 1.5 was used to produce and analyze the anti-B7-H7 fully human IgG antibody obtained in Example 1.6. Tables 1-3 and 1-4 list the results of small-volume and large-volume transient expression purification, respectively. Anti-B7-H7 antibody sequences (Tables 1-5) were also obtained from previous literature and used as controls in subsequent experiments.

[0140] [Table 3]

[0141] [Table 4]

[0142] [Table 5]

[0143] Example 1.7. Anti-B7-H7 Antibody Sequences and Numbers The amino acid sequences of the CDRs of the antibodies obtained in the present invention are as shown in the table below, and all of these CDRs are shown according to the Chothia definition rules.

[0144] [Table 6] Here, Laa-Lbb may refer to the amino acid sequence from position aa (Chothia numbering rules) to position bb (Chothia numbering rules) from the N-terminus of the antibody light chain, and Haa-Hbb may refer to the amino acid sequence from position aa (Chothia numbering rules) to position bb (Chothia numbering rules) from the N-terminus of the antibody heavy chain. For example, L24-L34 may refer to the amino acid sequence from position 24 to 34 according to the Chothia numbering rules from the N-terminus of the antibody light chain, and H26-H35 may refer to the amino acid sequence from position 26 to 35 according to the Chothia numbering rules from the N-terminus of the antibody heavy chain. As will be appreciated by those skilled in the art, when encoding CDRs with Chothia, there may be insertion sites at several positions (see http: / / bioinf.org.uk / abs / ).

[0145] Tables 1-7-1 and 1-7-2 list the sequence numbers corresponding to the sequences of the anti-B7-H7 antibodies of the present invention and the control antibody molecules.

[0146] [Table 7-1] [Table 7-2] [Table 7-3]

[0147] [Table 8-1] [Table 8-2]

[0148] Example 2. Detection of the binding ability of B7-H7 antibody to B7-H7 by FACS This example is to study the in vitro binding activity of anti-human B7-H7 H2L2 monoclonal antibody to human / cynomolgus monkey B7-H7. Since there is no homologous molecule of B7-H7 in mice, detection was not performed. Antibody binding experiments at the cellular level were performed using HEK-293 cell line overexpressing human B7-H7 (HEK-293 / hu B7-H7, Wahak Pharmaceuticals), HEK-293 cell line overexpressing cynomolgus monkey B7-H7 (HEK-293 / cyno B7-H7, Wahak Pharmaceuticals), or cell lines HCC827 (ATCC® CRL-2868) and LS180 (Nanjing Kebai, CBP60034) that highly express human B7-H7. Briefly, HEK-293 / hu B7-H7 cells, HEK-293 / cyno B7-H7 cells, HCC827 cells, or LS180 cells were digested and resuspended in PBS containing 2% BSA at a cell density of 1 × 10 6The cells were adjusted to 100 μL / mL. 100 μL cells / well were seeded into a 96-well V-bottom plate (Corning, #3894), and then 100 μL / well of the detection antibody, which was serially diluted at 3-fold concentration, twice the final concentration, was added. The cells were incubated at 4°C for 2 hours, protected from light. Then, 100 μL / well of pre-cooled 2% BSA in PBS was added, the cells were rinsed twice, centrifuged at 500 g for 5 minutes at 4°C, and the supernatant was discarded. Next, fluorescent secondary antibody (Alexa Fluor 488-conjugated AffiniPure Goat Anti-Human IgG, Fcγ Fragment Specific, Jackson, #109-545-098, diluted 1:500) was added at 100 μL / well, and incubated at 4°C for 1 hour, protected from light. The cells were washed twice with 100 μL / well of pre-chilled PBS containing 2% BSA, centrifuged at 500 g for 5 min at 4°C, and the supernatant was discarded. Finally, the cells were resuspended with 200 μL / well of pre-chilled PBS containing 2% BSA, and the fluorescence signal was read using an ACEA Novocyte3000 flow cytometer.

[0149] The binding of antibodies to human B7-H7 on the cell surface, cynomolgus monkey B7-H7, and B7-H7 on the tumor cell surface of HCC827 and LS180 is summarized below (Tables 2-1, 2-2, and 2-3).

[0150] [Table 9] ~ indicates that binding was too weak to fit the curve and therefore the maximum MFI and EC50 could not be calculated.

[0151] [Table 10] ~ indicates that binding was too weak to fit the curve and therefore the maximum MFI and EC50 could not be calculated.

[0152] [Table 11] The results of primary antibody binding cell surface human B7-H7 are shown in Figure 1A-F. The results show that these primary antibodies have excellent binding activity to human and cynomolgus B7-H7, and can bind to tumor cell surface B7-H7. LALA mutation engineering was performed on the Fc terminus of PR003181, PR003249, PR003259, and PR003264 to eliminate ADCC effect, and the results show that the engineered antibodies PR004260, PR004261, PR004262, and PR004263 have cell binding activity consistent with the primary antibodies (Figure 2). Furthermore, PTM was removed from PR004261 and PR004262 to obtain antibodies PR004479-PR004494, and the FACS results show that their binding activity is substantially consistent with the primary antibodies (Figure 3).

[0153] Example 3. Antibody blocking of binding of human B7-H7 protein to HEK293 cells overexpressing human CD28H The purpose of this study was to study the activity of human anti-B7-H7 antibodies in blocking the binding of human B7-H7 to its receptor CD28H in vitro. Human B7-H7 / human CD28H binding blocking experiments at the cellular level were performed using a HEK-293 cell line overexpressing human CD28H (HEK-293 / CD28H, Wahak Pharmaceuticals). Briefly, HEK-293 / CD28H cells were digested and resuspended in PBS containing 2% BSA. The cell density was 1 × 10 6The cells were adjusted to 100 μL / well. 100 μL cells / well were seeded into a 96-well V-bottom plate (Corning, Cat#:3894), followed by adding 100 μL / well of the antigen-binding protein to be detected, which was serially diluted at 3-fold concentration, which is twice the final concentration, and mixing evenly, where the highest concentration of the antigen-binding protein was 100 nM, with a total of 8 concentrations, and hIgG was used as a control. The cells were incubated at 4°C for 1 hour in the dark. Then, the cells were centrifuged at 4°C for 5 minutes, the supernatant was discarded, and then 50 μL / well of biotin-labeled human B7-H7 protein (Acro Biosystems, B77-H82F5) at a concentration of 1 μg / mL was added, and incubated at 4°C for 30 minutes in the dark. Pre-cooled 2% BSA-containing PBS was added at 100 μL / well, the cells were rinsed twice, centrifuged at 500 g for 5 minutes at 4°C, and the supernatant was discarded. Fluorescent secondary antibody (PE Streptavidin, BD, Cat#:554061, 1:200) was added at 100 μL / well and incubated at 4°C, protected from light, for 30 min. Cells were washed twice with 200 μL / well pre-chilled PBS, centrifuged at 500g for 5 min at 4°C, and the supernatant was discarded. Finally, cells were resuspended with 200 μL / well pre-chilled PBS, and the fluorescent signal values ​​were read using an ACEA Novocyte3000 flow cytometer. IC50 was calculated.

[0154] The results are shown in Figure 4 and Table 3. The blocking efficiency of PR003251, PR003254, PR003260, PR003262, PR003263, and PR003181 was not poor, and the other antibodies could completely block the binding of B7-H7 protein to its receptor CD28H, all of which were superior to the positive control PR003181.

[0155] [Table 12]

[0156] Example 4. Antibody blocking of binding of human B7-H7 protein to human KIR3DL3 protein and CHO-K1 cells overexpressing KIR3DL3 Example 4.1. Antibody blocking of binding of human B7-H7 protein to KIR3DL3 expressed on the cell surface The purpose of this study was to study the activity of human anti-B7-H7 antibodies in blocking the binding of human B7-H7 to its receptor KIR3DL3 in vitro. Human KIR3DL3-overexpressing CHO-K1 cells (CHO-K1 / KIR3DL3, Wahak Pharmaceuticals) were used to perform human B7-H7 / human KIR3DL3 binding blocking experiments at the cellular level. Briefly, CHO-K1 / KIR3DL3 cells were digested and resuspended in PBS containing 2% BSA. The cell density was 1x10 6 The cells were adjusted to 100 μL / well. 100 μL cells / well were seeded into a 96-well V-bottom plate (Corning, Cat#:3894), followed by adding 100 μL / well of the antigen-binding protein to be detected, which was serially diluted at 3-fold concentration, which is twice the final concentration, and mixing evenly, where the highest concentration of the antigen-binding protein was 100 nM, with a total of 8 concentrations, and hIgG was used as a control. The cells were incubated at 4°C for 1 hour in the dark. Then, the cells were centrifuged at 4°C for 5 minutes, the supernatant was discarded, and then 50 μL / well of biotin-labeled human B7-H7 protein (Acro Biosystems, B77-H82F5) at a concentration of 1 μg / mL was added, and incubated at 4°C for 30 minutes in the dark. Pre-cooled 2% BSA-containing PBS was added at 100 μL / well, the cells were rinsed twice, centrifuged at 500 g for 5 minutes at 4°C, and the supernatant was discarded. Fluorescent secondary antibody (PE Streptavidin, BD, Cat#:554061, 1:200) was added at 100 μL / well and incubated at 4°C, protected from light, for 30 min. Cells were washed twice with 200 μL / well pre-chilled PBS, centrifuged at 500g for 5 min at 4°C, and the supernatant was discarded. Finally, cells were resuspended with 200 μL / well pre-chilled PBS, and the fluorescent signal values ​​were read using an ACEA Novocyte3000 flow cytometer. IC50 was calculated.

[0157] The results are shown in FIG. 5 and Table 4, and demonstrate that, except for the control IgG, all of the antibodies were able to completely block the binding of B7-H7 protein to its receptor KIR3DL3.

[0158] [Table 13]

[0159] Example 4.2. Antibody blocking of binding between human B7-H7 protein and human KIR3DL3 protein Human KIR3DL3 (Sino Biological, Cat# 16055-H08H) was diluted to 5 μg / ml in PBS and added to a 96-well plate (Corning, cat# 9018) at 100 μl / well and incubated at 4°C overnight. After discarding the liquid, the plate was washed three times with PBS buffer, and 200 μl of PBS mounting solution containing 1% BSA was added and incubated at room temperature for 1 hour. The mounting solution was discarded and the plate was washed three times with PBS buffer. Different concentrations of detection antibodies and 6 μg / ml biotin-B7H7 protein (Acro Biosystems, Cat# B77-H82F5) or Biotin-B7H4 protein (Acro Biosystems, Cat# B74-H82E2) were added. Biotin-B7H4 protein is a negative control protein and does not bind to KIR3DL3. Starting from a concentration of 100 nM, the detection target antibody was diluted in 3-fold concentration in a total of eight concentration gradients. 100 μl was added per well and incubated overnight at 4 ° C. After washing three times with PBS buffer, 500-fold diluted StrepTactin-HRP Conjugate (Bio-rad, Cat# 161-0380) was added and incubated for 1 hour under the condition of 37 ° C in the dark. After washing four times with PBS buffer, TMB (KPL SureBlue, Cat# 5120-0077) was added at 100 μL / well, and the plate was left at room temperature for about 10 minutes in the dark, and the reaction was stopped by adding 100 μL / well of stop solution (BBI life sciences, Cat# E661006-0200) to each well, and the plate was placed in a plate reader (PerkinElemer # Enspire) to measure the 450 nm absorbance value.

[0160] The results are shown in Figure 6, in which B7-H7 protein can bind to KIR3DL3 protein in the absence of antibody, while B7-H4 protein does not bind, and the detection antibodies PR004261, PR004262, and PR004263 can block the binding between B7-H7 protein and KIR3DL3 protein in a dose-dependent manner.

[0161] Example 5. Detection of T cell activation activity To detect the function of anti-B7-H7 antibody in activating T cells by blocking T cell immune checkpoints, this experiment used anti-human CD3 antibody OKT3, which overexpresses full-length B7-H7 and scFv form in CHO-K1 cells, as artificial antigen-presenting cells (CHO-K1 / OS8 / hB7-H7, Beijing Hongyuan) or negative control cells (CHO-K1 / OS8, Beijing Hongyuan), and used a human T cell isolation kit (Miltenyi, # 130-096-535) to isolate T cells according to the method in the instruction manual, and then co-cultured the artificial antigen-presenting cells and T cells to detect the effect of anti-B7-H7 antibody on T cell activation. Specifically, CHO-K1-OS8-hB7-H7 or control cells CHO-K1-OS8 were cultured at 1 × 10 4 Human primary T cells were isolated at a density of 2 × 10 / well and cultured overnight. 5The cells were added to CHO-K1-OS8-hB7-H7 cells at a density of 100μl / well. Then, the detection antibody, which was serially diluted with 3x concentration of 2x final concentration, was added at 100μL / well, where the highest antibody final concentration was 10nM, and there were a total of 6 concentrations for each antibody, with two duplicates. After culturing for 3 days, the supernatant was collected and the concentration of IFN-γ was detected by ELISA method. The results are shown in Figure 7, where Figures 7A to 7H show that antibodies PR003248, PR003249, PR003250, PR003252, PR003259, PR003261, PR003264, PR003266 and the control antibody have high activity in promoting T cell activation and secreting IFN-γ (wherein A to D are donor 1 and E to H are donor 2), and Figure 7I shows that PR004260, PR004261, PR004262, and PR004263 also have high activity in promoting secretion of IFN-γ from T cells. If the artificial antigen-presenting cells did not express B7-H7, the antibody did not exhibit activity in promoting T cell activation, suggesting that the action of the antibody was specific to B7-H7 (Figure 8 shows the results showing that the B7-H7 antibody does not act on B7-H7-negative cells and cannot activate T cells).

[0162] Example 6. Detection of NK cell killing activity To detect the function of anti-B7-H7 antibody in activating NK cells, this experiment used MDA-MB-231 cells overexpressing full-length B7-H7 as target cells (MDA-MB-231 / hB7-H7, Wahak Pharmaceuticals), isolated NK cells using a human NK cell isolation kit (Miltenyi, #130-092-657) according to the instructions in the manual, and activated the isolated and purified NK cells with 100 IU / ml interleukin-2 for 2 days. The target cells MDA-MB-231 / hB7-H7 were digested with pancreatin and stained with 1uM cell tracking dye CFSE for 10 minutes at room temperature in the dark. The activated NK cells were co-cultured with the target cells, and the detection target B7H7 antibody was added and incubated in a 37℃ incubator for 4h. After the incubation was completed, 2 μl of 7AAD dead cell dye was added to each well, the cells were mixed evenly with a pipette, and analyzed by a flow cytometer BD CantoII within 10 minutes to detect the killing of target cells. (Target cell killing (%) = 7AAD + CFSE + double positive cells / CFSE + positive cells) The results are shown in Figure 9 and demonstrate that, compared to the isotype control, antibody PR004263 significantly enhanced target cell killing by NK cells in a dose-dependent manner.

[0163] Example 7. Measurement of affinity between anti-B7-H7 antibodies and human B7-H7 recombinant protein Affinity measurement by BLI method 10x kinetic buffer (ForteBio, #18-1105) was diluted to 1x and used for affinity testing and dilution of antigen and antibody. Kinetic analysis of antigen-antibody binding was performed using Biolayer Interference (BLI) technology with Octet Red 96e (Fortebio) molecular interaction analyzer.

[0164] When measuring the affinity between antigen and antibody, the rotation speed of the sensor is 1000 rpm. First, AHC sensors (Fortebio, #18-5060) arranged in a row were equilibrated in the test buffer for 10 minutes, and then the B7-H7 antibody was captured by the AHC sensor at a capture height of 0.7 nm. After the AHC sensor was equilibrated in the buffer for 120 s, it was bound to two-fold serially diluted human B7-H7 (concentrations of 50 to 3.125 nm and 0 nm) for 180 s and dissociated for 300 s. Finally, the AHC sensor was regenerated by immersing it in a 10 mm glycine-HCl pH 1.5 solution, and the proteins bound to the sensor were eluted.

[0165] When analyzing the data with Octet Data Analysis software (Fortebio, version 11.0), 0 nm was used as the reference well, the reference signal (reference subtraction) was removed, and the “1:1 Global fitting” method was selected to perform data fitting and calculate the kinetic parameters of the binding between the antigen and the antigen-binding protein, k on (1 / Ms) value, k dis (1 / s) value and K D (M) values ​​were obtained, and the results are shown in Table 5.

[0166] [Table 14]

[0167] Example 8. Measurement of epitope competition of anti-B7-H7 antibody binding to B7-H7 by BLI method Epitope competition experiments were performed on B7-H7 antibody using ForteBio Octet Red96e platform, and the experiment buffer was the same as above. Step 1, acquisition of 100% signal of antibody: B7-H7 (Acro Biosystems, B77-H82F5) was captured using SA sensor (Fortebio, #18-5019), and the capture height was 0.25 nm. After the sensor was equilibrated in the buffer for 120 s, it was subjected to each antibody diluted to 100 nm for 240 s, and the final signal of the binding of the antibody with B7-H7 was recorded as the 100% signal of the antibody. Step 2, epitope competition experiment: B7-H7 was captured with SA sensor, and the capture height was 0.25 nm. The sensor was immersed in the first antibody (concentration 100 nm) for 240 s, then the SA sensor was immersed in a mixture of the first antibody and the second antibody (final concentration of both antibodies is 100 nm) for 240 s, and the signal difference after immersing the sensor in the antibody mixture was recorded as the signal of the antibody as the second antibody. The inhibition rate was calculated by the following formula: Inhibition rate (%) = (AB) / A*100 A: 100% signal of an antibody (obtained from step 1), B: signal of the same antibody as the second antibody (obtained from step 2).

[0168] If the inhibition rate is greater than 85%, it means that the epitopes bound by the two antibodies completely overlap, and if the inhibition rate is less than 85%, it means that the epitopes bound by the two antibodies do not completely overlap.

[0169] First, PR003249 was used as the first antibody, and other antibodies were used as the second antibody to detect their competition with it (PR003249 in the second antibody includes three overlaps). According to the results in Table 6-1, the second antibodies PR003248, PR003250, PR003252, PR003259, PR003261, PR003264, PR003265, and PR003266 completely compete with the first antibody PR003249, suggesting that they belong to the same first binding epitope, and the control antibody PR003181 partially overlaps with it. For the remaining different epitope antibodies, PR003251 was used as the first antibody and the other antibodies were used as the second antibody to compete with it, and the results in Table 6-2 show that PR003251, PR003254, PR003260, PR003262, and PR003263 completely compete with each other, suggesting that they belong to the same binding epitope, whereas the control antibody PR003181 does not overlap with it. The epitopes of the antibodies binding to B7-H7 are summarized in Table 6-3.

[0170] [Table 15]

[0171] [Table 16]

[0172] [Table 17]

[0173] Example 9. Cross-reactivity with other members of the B7 family B7 family proteins (see Table 7 for details) were each diluted to 1 μg / mL with PBS, added to a 96-well plate (Corning, #9018) at 100 μl / well, and incubated at 4°C overnight. After discarding the liquid, the plate was washed three times with PBST buffer (pH 7.4, containing 0.05% Tween-20), 250 μl of 2% BSA mounting solution was added, and incubated at 37°C for 1 hour. The mounting solution was discarded, the plate was washed three times with PBST buffer (pH 7.4, containing 0.05% Tween-20), and the antigen-binding protein to be detected was diluted to two concentrations, 10 nm and 1 nm, added to each well at 100 μl, and incubated at 37°C for 1 hour. An isotype antibody was used as a control. After washing three times with PBST buffer (pH 7.4, containing 0.05% Tween-20), a 5000-fold diluted sheep anti-human HRP secondary antibody (Invitrogen, #A18805) was added and incubated at 37°C under the condition of shading for 1 hour. After washing three times with PBST buffer (pH 7.4, containing 0.05% Tween-20), 100 μl / well of TMB (Biopanda, #TMB-S-003) was added and left at room temperature for about 30 minutes under the shade, and 50 μl / well of stop solution (BBI life sciences, #E661006-0200) was added to each well to stop the reaction, and the plate was placed in a plate reader (PerkinElemer, #Enspire) to measure the 450 nm absorbance (OD450) value. Figure 10 shows that the antibody of the present invention specifically binds only to B7-H7 protein and does not cross-react with other member proteins of the B7 family.

[0174] [Table 18]

[0175] Example 10. Serum stability analysis Thirty microliters of antibody was taken and diluted in 270 μl of normal human serum (serum concentration 90%), and the antibody was divided into five portions, incubated at 37°C for 0, 1, 4, 7, and 14 days, respectively, removed, flash frozen in liquid nitrogen, and stored at -80°C. The binding of the antibody to B7-H7 in HEK-293 / hB7-H7 cells was detected by flow cytometry. HEK-293 / hB7-H7 cells were digested and resuspended in PBS containing 2% BSA. The cell density was adjusted to 1 × 10 6 The cells were adjusted to 1:500 cells / mL. 100 μL cells / well were seeded into a 96-well V-bottom plate (Corning, #3894), and then 100 μL / well of the detection antibody, which was serially diluted at 3-fold concentration, twice the final concentration, was added. The cells were incubated at 4°C for 2 hours, protected from light. Then, 100 μL / well of pre-cooled 2% BSA in PBS was added, the cells were rinsed twice, centrifuged at 500g for 5 minutes at 4°C, and the supernatant was discarded. 100 μL / well of fluorescent secondary antibody (Alexa Fluor 488-conjugated AffiniPure Goat Anti-Human IgG, Fcγ Fragment Specific, Jackson, #109-545-098, diluted 1:500) was added and incubated at 4°C for 60 minutes, protected from light. The cells were washed twice with 100μL / well of pre-chilled PBS containing 2% BSA, centrifuged at 500g for 5 min at 4℃, and the supernatant was discarded. Finally, the cells were resuspended with 200μL / well of pre-chilled PBS containing 2% BSA, and the fluorescence signal values ​​were read using ACEA Novocyte3000 flow cytometry. The results in Figure 11 showed that PR004261, PR004262, and PR004263 have excellent stability in human serum at 37℃ for 14 days.

[0176] Example 11. Antitumor effect of anti-B7-H7 antibody MDA-MB-231 tumor model in NCG mice with reconstituted human PBMC immune system On the day of cell inoculation, each NCG mouse was inoculated with 5 × 10 6The cells were then resuspended in a mixture of PBS and Matrigel (1:1) (0.1 mL / mouse) and inoculated subcutaneously. The average tumor volume in the mice was approximately 90 mm 3 If the number of mice reached 10, the mice were divided into 4 groups of 24 mice, with each group receiving 5 × 10 6 Human PBMCs were inoculated intravenously, and the cells were resuspended in 200 μl of PBS. Administration began the following day, with a twice-weekly administration cycle for a total of 4 weeks, and the effects of PR004261, PR004262, and PR004263 antibodies at a dose of 20 MPK were tested by intravenous administration into the tail vein. After the start of administration, body weight and tumor volume were measured twice a week, and the tumor volume was calculated using the following formula: tumor volume (mm 3 ) = 0.5 × tumor long axis × tumor short axis 2 The experimental observations were terminated on the 36th day after administration, after which all mice were euthanized.

[0177] The in vivo antitumor effect of the MDA-MB-231 / hB7-H7 tumor model of the NCG mouse reconstituted human PBMC immune system is shown in FIG. 12A. Specifically, the vehicle control group mice had a mean tumor volume of 339 mm on day 32 after administration. 3 In the treatment group with the test drug PR004261 (20 mg / kg), the mean tumor volume was 192 mm on the 32nd day after administration. 3 The tumor inhibition rate (TGI) (%) was 43.43%, which was significantly different from the vehicle control group (p value < 0.0001). The treatment group with the test drug PR004262 (20 mg / kg) had a mean tumor volume of 229 mm on the 32nd day after administration. 3 The tumor inhibition rate (TGI) (%) was 32.52%, which was significantly different from the vehicle control group (p value was 0.0049). The treatment group with the test drug PR004263 (20 mg / kg) had a mean tumor volume of 86 mm on the 32nd day after administration. 3 Compared to the vehicle control group, there was a significant difference (p value < 0.0001), with a tumor inhibition rate (TGI) (%) of 74.57%.

[0178] In the second experiment, a similar tumor inoculation schedule was used, with a dosing cycle of twice a week for a total of three weeks, and the effect of PR004263 antibody was tested at three doses, 5MPK, 10MPK, and 20MPK, administered intraperitoneally. After the start of dosing, body weight and tumor volume were measured twice a week, and the formula for calculating tumor volume was: tumor volume (mm 3 ) = 0.5 × tumor long axis × tumor short axis 2 The experimental observations were terminated on the 36th day after administration, after which all mice were euthanized.

[0179] For the in vivo antitumor effect of the tumor model, see FIG. 12B. Specifically, the vehicle control group mice had a mean tumor volume of 618 mm on the 26th day after inoculation. 3 In the treatment group with the test drug PR004263 (5 mg / kg), the mean tumor volume was 420 mm on the 26th day after inoculation. 3 The mean tumor volume in the PR004263 (10 mg / kg) treatment group was 243 mm on the 26th day after inoculation, which was significantly different from the vehicle control group (p value < 0.0198) and the tumor inhibition rate (TGI) (%) was 32.1%. 3 The tumor inhibition rate (TGI) (%) was 60.65%, which was significantly different from the vehicle control group (p value was 0.0001). The treatment group with the test drug PR004263 (20 mg / kg) had a mean tumor volume of 219 mm on the 26th day after inoculation. 3 Compared to the vehicle control group, there was a significant difference (p value < 0.0001), with a tumor inhibition rate (TGI) (%) of 64.52%.

[0180] NUGC-4 and HCC-827 tumor models in NCG mice with reconstituted human PBMC immune system Both NUGC-4 and HCC-827 tumor cells endogenously express B7-H7. In vivo pharmacodynamics studies were conducted using the NUGC-4 tumor model in NCG mice with reconstituted human PBMC immune system. The specific method is as follows: On the day of cell inoculation, a total of 5 × 10 6 NUGC-4 tumor cells and 1 x 10 6 The mice in each group had an average tumor volume of 70 mm. 3When the mice reached a certain level of toxicity, they were divided into groups and administered the drug intraperitoneally for a total of six doses. After the start of administration, the body weight and tumor volume were measured twice a week, and the tumor volume was calculated as follows: tumor volume (mm 3 ) = 0.5 × tumor long axis × tumor short axis 2 Data analysis was performed using t-test. The in vivo antitumor effect of the NCG mouse reconstituted human PBMC immune system in the NUGC-4 tumor model is shown in FIG. 12C. Specifically, the antibody control group mice had an average tumor volume of 1140.62 mm on the 26th day after administration. 3 In the treatment group with the test drug PR004263 (10 mg / kg), the mean tumor volume was 491.38 mm on the 26th day after administration. 3 The mean tumor volume in the 20 mg / kg treatment group was 191.99 mm on the 26th day after administration, which was significantly different from the vehicle control group (p value < 0.05) with a tumor inhibition rate (TGI) of 56.92%. 3 Compared with the vehicle control group, there was a significant difference (p value < 0.01), with a tumor inhibition rate TGI (%) of 83.17%.

[0181] An in vivo pharmacodynamics study was carried out using the HCC-827 tumor model in NCG mice with reconstituted human PBMC immune system. The specific method is as follows: on the day of cell inoculation, 1 × 10 7 HCC-827 cells were inoculated subcutaneously. The average tumor volume in each mouse was approximately 110 mm. 3 If the number of mice is 5 × 10, the mice are divided into groups. 6 The mice were intravenously inoculated with human PBMCs, and administration was started the next day. The administration cycle was twice a week for a total of five doses, and the administration method was intraperitoneal injection. After the start of administration, the body weight and tumor volume were measured twice a week, and the tumor volume was calculated using the following formula: tumor volume (mm 3 ) = 0.5 × tumor long axis × tumor short axis 2 The experimental observation was terminated on the 26th day after administration, and all mice were then euthanized. The in vivo antitumor effect of the NCG mouse reconstituted human PBMC immune system in the HCC-827 tumor model is shown in FIG. 12D. Specifically, the antibody control group mice had an average tumor volume of 1020.74 mm on the 26th day after administration. 3In the treatment group with the test drug PR004263 (10 mg / kg), the mean tumor volume was 778.35 mm on the 26th day after administration. 3 The mean tumor volume in the 20 mg / kg treatment group was 597.69 mm on the 26th day after administration, which was significantly different from the vehicle control group (p value < 0.05) with a tumor inhibition rate (TGI) of 23.75%. 3 Compared with the vehicle control group, there was a significant difference (p value < 0.01), with a tumor inhibition rate (TGI) (%) of 41.45%.

Claims

1. 1. An anti-B7-H7 antibody, or antigen-binding fragment thereof, comprising a light chain variable region (VL) and a heavy chain variable region (VH), wherein: The VL comprises a complementarity determining region (CDR) of LCDR1 represented by the amino acid sequence of SEQ ID NO: 82, an LCDR2 represented by the amino acid sequence of any one of SEQ ID NOs: 94 to 100, and an LCDR3 represented by the amino acid sequence of any one of SEQ ID NOs: 111, 112, 114 to 116, 120, and 121, or a mutation thereof; The VH comprises a CDR having an HCDR1 represented by the amino acid sequence of SEQ ID NO: 7, an HCDR2 represented by the amino acid sequence of SEQ ID NO: 34 or 36, and an HCDR3 represented by any one of the amino acid sequences of SEQ ID NO: 57 to 68, or a mutation thereof; wherein the mutation comprises an insertion, deletion or substitution of 3, 2 or 1 amino acids in the amino acid sequence of the CDR of the anti-B7-H7 antibody or antigen-binding fragment thereof.

2. The LCDR1 mutation comprises three, two or one of the following amino acid substitutions in the amino acid sequence shown in SEQ ID NO: 82: S5G, I6V / F, S7N, S8N / Y, W9N / Y and L10F, which amino acid sequence is preferably as shown in any one of SEQ ID NOs: 81, 83 to 88; and / or The LCDR3 mutation has one of the following amino acid substitutions in the amino acid sequence shown in SEQ ID NO: 112: N4Q, S5A and Y8V; or has two or one of the following amino acid substitutions in the amino acid sequence shown in SEQ ID NO: 115: Q1H, N4Y, N5I / K and L8Y; or has one of the following amino acid substitutions in the amino acid sequence shown in SEQ ID NO: 116: N4Q and S5A, which amino acid sequence is preferably as shown in any one of SEQ ID NOs: 113, 117-119, 122-125; and / or The HCDR1 mutation has two or one of the following amino acid substitutions in the amino acid sequence shown in SEQ ID NO: 7: F2G and D6R / N / S / Y / T, and the amino acid sequence is preferably as shown in any one of SEQ ID NOs: 8 to 13; and / or The anti-B7-H7 antibody or antigen-binding fragment thereof according to claim 1, characterized in that the HCDR2 mutation has two or one amino acid substitutions selected from the group consisting of Y2F, D3N / E, G4E / A, S5N / T / R and N6E / D / K in the amino acid sequence shown in SEQ ID NO: 36, and the amino acid sequence is preferably as shown in any one of SEQ ID NOs: 27 to 33, 35, and 37 to 40.

3. the amino acid sequence of the LCDR1 is as set forth in SEQ ID NO: 87, the amino acid sequence of the LCDR2 is as set forth in SEQ ID NO: 97, and the amino acid sequence of the LCDR3 is as set forth in SEQ ID NO: 120; or the amino acid sequence of the LCDR1 is as set forth in SEQ ID NO: 82, the amino acid sequence of the LCDR2 is as set forth in SEQ ID NO: 94, and the amino acid sequence of the LCDR3 is as set forth in SEQ ID NO: 112; or the amino acid sequence of the LCDR1 is as set forth in SEQ ID NO: 82, the amino acid sequence of the LCDR2 is as set forth in SEQ ID NO: 94, and the amino acid sequence of the LCDR3 is as set forth in SEQ ID NO: 122; or the amino acid sequence of the LCDR1 is as set forth in SEQ ID NO: 82, the amino acid sequence of the LCDR2 is as set forth in SEQ ID NO: 94, and the amino acid sequence of the LCDR3 is as set forth in SEQ ID NO: 123; or the amino acid sequence of the LCDR1 is as set forth in SEQ ID NO: 85, the amino acid sequence of the LCDR2 is as set forth in SEQ ID NO: 97, and the amino acid sequence of the LCDR3 is as set forth in SEQ ID NO: 116; or the amino acid sequence of the LCDR1 is as set forth in SEQ ID NO: 85, the amino acid sequence of the LCDR2 is as set forth in SEQ ID NO: 97, and the amino acid sequence of the LCDR3 is as set forth in SEQ ID NO: 124; or the amino acid sequence of the LCDR1 is as set forth in SEQ ID NO: 85, the amino acid sequence of the LCDR2 is as set forth in SEQ ID NO: 97, and the amino acid sequence of the LCDR3 is as set forth in SEQ ID NO: 125; or the amino acid sequence of the LCDR1 is as set forth in SEQ ID NO: 81, the amino acid sequence of the LCDR2 is as set forth in SEQ ID NO: 94, and the amino acid sequence of the LCDR3 is as set forth in SEQ ID NO: 111; or the amino acid sequence of the LCDR1 is as set forth in SEQ ID NO: 82, the amino acid sequence of the LCDR2 is as set forth in SEQ ID NO: 94, and the amino acid sequence of the LCDR3 is as set forth in SEQ ID NO: 111; or the amino acid sequence of the LCDR1 is as set forth in SEQ ID NO: 82, the amino acid sequence of the LCDR2 is as set forth in SEQ ID NO: 94, and the amino acid sequence of the LCDR3 is as set forth in SEQ ID NO: 117; or the amino acid sequence of the LCDR1 is as set forth in SEQ ID NO: 82, the amino acid sequence of the LCDR2 is as set forth in SEQ ID NO: 96, and the amino acid sequence of the LCDR3 is as set forth in SEQ ID NO: 114; or the amino acid sequence of the LCDR1 is as set forth in SEQ ID NO: 83, the amino acid sequence of the LCDR2 is as set forth in SEQ ID NO: 95, and the amino acid sequence of the LCDR3 is as set forth in SEQ ID NO: 113; or the amino acid sequence of the LCDR1 is as set forth in SEQ ID NO: 83, the amino acid sequence of the LCDR2 is as set forth in SEQ ID NO: 98, and the amino acid sequence of the LCDR3 is as set forth in SEQ ID NO: 113; or the amino acid sequence of the LCDR1 is as set forth in SEQ ID NO: 83, the amino acid sequence of the LCDR2 is as set forth in SEQ ID NO: 99, and the amino acid sequence of the LCDR3 is as set forth in SEQ ID NO: 119; or the amino acid sequence of the LCDR1 is as set forth in SEQ ID NO: 84, the amino acid sequence of the LCDR2 is as set forth in SEQ ID NO: 95, and the amino acid sequence of the LCDR3 is as set forth in SEQ ID NO: 115; or the amino acid sequence of the LCDR1 is as set forth in SEQ ID NO: 86, the amino acid sequence of the LCDR2 is as set forth in SEQ ID NO: 95, and the amino acid sequence of the LCDR3 is as set forth in SEQ ID NO: 118; or The amino acid sequence of the LCDR1 is as set forth in SEQ ID NO: 88, the amino acid sequence of the LCDR2 is as set forth in SEQ ID NO: 100, and the amino acid sequence of the LCDR3 is as set forth in SEQ ID NO: 121; and / or the amino acid sequence of HCDR1 is as set forth in SEQ ID NO: 12, the amino acid sequence of HCDR2 is as set forth in SEQ ID NO: 34, and the amino acid sequence of HCDR3 is as set forth in SEQ ID NO: 66; or the amino acid sequence of HCDR1 is as set forth in SEQ ID NO: 7, the amino acid sequence of HCDR2 is as set forth in SEQ ID NO: 28, and the amino acid sequence of HCDR3 is as set forth in SEQ ID NO: 58; or the amino acid sequence of HCDR1 is as set forth in SEQ ID NO: 7, the amino acid sequence of HCDR2 is as set forth in SEQ ID NO: 37, and the amino acid sequence of HCDR3 is as set forth in SEQ ID NO: 58; or the amino acid sequence of HCDR1 is as set forth in SEQ ID NO: 7, the amino acid sequence of HCDR2 is as set forth in SEQ ID NO: 38, and the amino acid sequence of HCDR3 is as set forth in SEQ ID NO: 58; or the amino acid sequence of HCDR1 is as set forth in SEQ ID NO: 9, the amino acid sequence of HCDR2 is as set forth in SEQ ID NO: 27, and the amino acid sequence of HCDR3 is as set forth in SEQ ID NO: 63; or the amino acid sequence of HCDR1 is as set forth in SEQ ID NO: 9, the amino acid sequence of HCDR2 is as set forth in SEQ ID NO: 39, and the amino acid sequence of HCDR3 is as set forth in SEQ ID NO: 63; or the amino acid sequence of HCDR1 is as set forth in SEQ ID NO: 9, the amino acid sequence of HCDR2 is as set forth in SEQ ID NO: 40, and the amino acid sequence of HCDR3 is as set forth in SEQ ID NO: 63; or the amino acid sequence of HCDR1 is as set forth in SEQ ID NO: 7, the amino acid sequence of HCDR2 is as set forth in SEQ ID NO: 27, and the amino acid sequence of HCDR3 is as set forth in SEQ ID NO: 57; or the amino acid sequence of HCDR1 is as set forth in SEQ ID NO: 7, the amino acid sequence of HCDR2 is as set forth in SEQ ID NO: 28, and the amino acid sequence of HCDR3 is as set forth in SEQ ID NO: 59; or the amino acid sequence of HCDR1 is as set forth in SEQ ID NO: 7, the amino acid sequence of HCDR2 is as set forth in SEQ ID NO: 36, and the amino acid sequence of HCDR3 is as set forth in SEQ ID NO: 68; or the amino acid sequence of HCDR1 is as set forth in SEQ ID NO: 8, the amino acid sequence of HCDR2 is as set forth in SEQ ID NO: 29, and the amino acid sequence of HCDR3 is as set forth in SEQ ID NO: 60; or the amino acid sequence of HCDR1 is as set forth in SEQ ID NO: 8, the amino acid sequence of HCDR2 is as set forth in SEQ ID NO: 30, and the amino acid sequence of HCDR3 is as set forth in SEQ ID NO: 62; or the amino acid sequence of HCDR1 is as set forth in SEQ ID NO: 8, the amino acid sequence of HCDR2 is as set forth in SEQ ID NO: 32, and the amino acid sequence of HCDR3 is as set forth in SEQ ID NO: 62; or the amino acid sequence of HCDR1 is as set forth in SEQ ID NO: 9, the amino acid sequence of HCDR2 is as set forth in SEQ ID NO: 27, and the amino acid sequence of HCDR3 is as set forth in SEQ ID NO: 61; or the amino acid sequence of HCDR1 is as set forth in SEQ ID NO: 9, the amino acid sequence of HCDR2 is as set forth in SEQ ID NO: 31, and the amino acid sequence of HCDR3 is as set forth in SEQ ID NO: 64; or the amino acid sequence of HCDR1 is as set forth in SEQ ID NO: 10, the amino acid sequence of HCDR2 is as set forth in SEQ ID NO: 29, and the amino acid sequence of HCDR3 is as set forth in SEQ ID NO: 62; or the amino acid sequence of HCDR1 is as set forth in SEQ ID NO: 11, the amino acid sequence of HCDR2 is as set forth in SEQ ID NO: 33, and the amino acid sequence of HCDR3 is as set forth in SEQ ID NO: 65; or The amino acid sequence of the HCDR1 is as shown in SEQ ID NO: 13, the amino acid sequence of the HCDR2 is as shown in SEQ ID NO: 35, and the amino acid sequence of the HCDR3 is as shown in SEQ ID NO: 67; Preferably, the anti-B7-H7 antibody or antigen-binding fragment thereof comprises: The amino acid sequences of LCDR1, LCDR2 and LCDR3 contained in the VL are as shown in SEQ ID NO: 87, 97 and 120, respectively, and the amino acid sequences of HCDR1, HCDR2 and HCDR3 contained in the VH are as shown in SEQ ID NO: 12, 34 and 66, respectively; or The amino acid sequences of LCDR1, LCDR2 and LCDR3 contained in the VL are as shown in SEQ ID NO: 82, 94 and 112, respectively, and the amino acid sequences of HCDR1, HCDR2 and HCDR3 contained in the VH are as shown in SEQ ID NO: 7, 28 and 58, respectively; or The amino acid sequences of LCDR1, LCDR2 and LCDR3 contained in the VL are as shown in SEQ ID NO: 82, 94 and 112, respectively, and the amino acid sequences of HCDR1, HCDR2 and HCDR3 contained in the VH are as shown in SEQ ID NO: 7, 37 and 58, respectively; or The amino acid sequences of LCDR1, LCDR2 and LCDR3 contained in the VL are as shown in SEQ ID NO: 82, 94 and 122, respectively, and the amino acid sequences of HCDR1, HCDR2 and HCDR3 contained in the VH are as shown in SEQ ID NO: 7, 37 and 58, respectively; or The amino acid sequences of LCDR1, LCDR2 and LCDR3 contained in the VL are as shown in SEQ ID NO: 82, 94 and 123, respectively, and the amino acid sequences of HCDR1, HCDR2 and HCDR3 contained in the VH are as shown in SEQ ID NO: 7, 37 and 58, respectively; or The amino acid sequences of LCDR1, LCDR2 and LCDR3 contained in the VL are as shown in SEQ ID NO: 82, 94 and 112, respectively, and the amino acid sequences of HCDR1, HCDR2 and HCDR3 contained in the VH are as shown in SEQ ID NO: 7, 38 and 58, respectively; or The amino acid sequences of LCDR1, LCDR2 and LCDR3 contained in the VL are as shown in SEQ ID NO: 82, 94 and 122, respectively, and the amino acid sequences of HCDR1, HCDR2 and HCDR3 contained in the VH are as shown in SEQ ID NO: 7, 38 and 58, respectively; or The amino acid sequences of LCDR1, LCDR2 and LCDR3 contained in the VL are as shown in SEQ ID NO: 82, 94 and 123, respectively, and the amino acid sequences of HCDR1, HCDR2 and HCDR3 contained in the VH are as shown in SEQ ID NO: 7, 38 and 58, respectively; or The amino acid sequences of LCDR1, LCDR2 and LCDR3 contained in the VL are as shown in SEQ ID NO: 82, 94 and 122, respectively, and the amino acid sequences of HCDR1, HCDR2 and HCDR3 contained in the VH are as shown in SEQ ID NO: 7, 28 and 58, respectively; or The amino acid sequences of LCDR1, LCDR2 and LCDR3 contained in the VL are as shown in SEQ ID NO: 82, 94 and 123, respectively, and the amino acid sequences of HCDR1, HCDR2 and HCDR3 contained in the VH are as shown in SEQ ID NO: 7, 28 and 58, respectively; or The amino acid sequences of LCDR1, LCDR2 and LCDR3 contained in the VL are as shown in SEQ ID NO: 85, 97 and 116, respectively, and the amino acid sequences of HCDR1, HCDR2 and HCDR3 contained in the VH are as shown in SEQ ID NO: 9, 27 and 63, respectively; or The amino acid sequences of LCDR1, LCDR2 and LCDR3 contained in the VL are as shown in SEQ ID NO: 85, 97 and 116, respectively, and the amino acid sequences of HCDR1, HCDR2 and HCDR3 contained in the VH are as shown in SEQ ID NO: 9, 39 and 63, respectively; or The amino acid sequences of LCDR1, LCDR2 and LCDR3 contained in the VL are as shown in SEQ ID NO: 85, 97 and 124, respectively, and the amino acid sequences of HCDR1, HCDR2 and HCDR3 contained in the VH are as shown in SEQ ID NO: 9, 39 and 63, respectively; or The amino acid sequences of LCDR1, LCDR2 and LCDR3 contained in the VL are as shown in SEQ ID NO: 85, 97 and 125, respectively, and the amino acid sequences of HCDR1, HCDR2 and HCDR3 contained in the VH are as shown in SEQ ID NO: 9, 39 and 63, respectively; or The amino acid sequences of LCDR1, LCDR2 and LCDR3 contained in the VL are as shown in SEQ ID NO: 85, 97 and 116, respectively, and the amino acid sequences of HCDR1, HCDR2 and HCDR3 contained in the VH are as shown in SEQ ID NO: 9, 40 and 63, respectively; or The amino acid sequences of LCDR1, LCDR2 and LCDR3 contained in the VL are as shown in SEQ ID NO: 85, 97 and 124, respectively, and the amino acid sequences of HCDR1, HCDR2 and HCDR3 contained in the VH are as shown in SEQ ID NO: 9, 40 and 63, respectively; or The amino acid sequences of LCDR1, LCDR2 and LCDR3 contained in the VL are as shown in SEQ ID NO: 85, 97 and 125, respectively, and the amino acid sequences of HCDR1, HCDR2 and HCDR3 contained in the VH are as shown in SEQ ID NO: 9, 40 and 63, respectively; or The amino acid sequences of LCDR1, LCDR2 and LCDR3 contained in the VL are as shown in SEQ ID NO: 85, 97 and 124, respectively, and the amino acid sequences of HCDR1, HCDR2 and HCDR3 contained in the VH are as shown in SEQ ID NO: 9, 27 and 63, respectively; or The amino acid sequences of LCDR1, LCDR2 and LCDR3 contained in the VL are as shown in SEQ ID NO: 85, 97 and 125, respectively, and the amino acid sequences of HCDR1, HCDR2 and HCDR3 contained in the VH are as shown in SEQ ID NO: 9, 27 and 63, respectively; or The amino acid sequences of LCDR1, LCDR2 and LCDR3 contained in the VL are as shown in SEQ ID NO: 81, 94 and 111, respectively, and the amino acid sequences of HCDR1, HCDR2 and HCDR3 contained in the VH are as shown in SEQ ID NO: 7, 27 and 57, respectively; or The amino acid sequences of LCDR1, LCDR2 and LCDR3 contained in the VL are as shown in SEQ ID NO: 82, 94 and 112, respectively, and the amino acid sequences of HCDR1, HCDR2 and HCDR3 contained in the VH are as shown in SEQ ID NO: 7, 28 and 59, respectively; or The amino acid sequences of LCDR1, LCDR2 and LCDR3 contained in the VL are as shown in SEQ ID NO: 83, 95 and 113, respectively, and the amino acid sequences of HCDR1, HCDR2 and HCDR3 contained in the VH are as shown in SEQ ID NO: 8, 29 and 60, respectively; or The amino acid sequences of LCDR1, LCDR2 and LCDR3 contained in the VL are as shown in SEQ ID NO: 82, 96 and 114, respectively, and the amino acid sequences of HCDR1, HCDR2 and HCDR3 contained in the VH are as shown in SEQ ID NO: 9, 27 and 61, respectively; or The amino acid sequences of LCDR1, LCDR2 and LCDR3 contained in the VL are as shown in SEQ ID NO: 84, 95 and 115, respectively, and the amino acid sequences of HCDR1, HCDR2 and HCDR3 contained in the VH are as shown in SEQ ID NO: 10, 29 and 62, respectively; or The amino acid sequences of LCDR1, LCDR2 and LCDR3 contained in the VL are as shown in SEQ ID NO: 83, 98 and 113, respectively, and the amino acid sequences of HCDR1, HCDR2 and HCDR3 contained in the VH are as shown in SEQ ID NO: 8, 30 and 62, respectively; or The amino acid sequences of LCDR1, LCDR2 and LCDR3 contained in the VL are as shown in SEQ ID NO: 82, 94 and 117, respectively, and the amino acid sequences of HCDR1, HCDR2 and HCDR3 contained in the VH are as shown in SEQ ID NO: 9, 31 and 64, respectively; or The amino acid sequences of LCDR1, LCDR2 and LCDR3 contained in the VL are as shown in SEQ ID NO: 86, 95 and 118, respectively, and the amino acid sequences of HCDR1, HCDR2 and HCDR3 contained in the VH are as shown in SEQ ID NO: 8, 32 and 62, respectively; or The amino acid sequences of LCDR1, LCDR2 and LCDR3 contained in the VL are as shown in SEQ ID NO: 83, 99 and 119, respectively, and the amino acid sequences of HCDR1, HCDR2 and HCDR3 contained in the VH are as shown in SEQ ID NO: 11, 33 and 65, respectively; or The amino acid sequences of LCDR1, LCDR2 and LCDR3 contained in the VL are as shown in SEQ ID NO: 88, 100 and 121, respectively, and the amino acid sequences of HCDR1, HCDR2 and HCDR3 contained in the VH are as shown in SEQ ID NO: 13, 35 and 67, respectively; or The amino acid sequences of LCDR1, LCDR2, and LCDR3 contained in the VL are as shown in SEQ ID NOs: 82, 94, and 111, respectively, and the amino acid sequences of HCDR1, HCDR2, and HCDR3 contained in the VH are as shown in SEQ ID NOs: 7, 36, and 68, respectively. The anti-B7-H7 antibody or antigen-binding fragment thereof according to claim 1 or 2.

4. The light chain variable region (VL) further comprises a light chain variable region framework region (VL FWR), and / or the heavy chain variable region (VH) further comprises a heavy chain variable region framework region (VH FWR), wherein The VL FWR is a human antibody light chain variable region framework region, and the VH FWR is a human antibody heavy chain variable region framework region; Preferably, The VL FWR includes VL FWR1 having an amino acid sequence shown in any one of SEQ ID NOs: 74 to 79, VL FWR2 having an amino acid sequence shown in any one of SEQ ID NOs: 90 to 92, VL FWR3 having an amino acid sequence shown in any one of SEQ ID NOs: 102 to 109, and VL FWR4 having an amino acid sequence shown in any one of SEQ ID NOs: 127 to 130; and / or the VH FWR includes VH FWR1 having an amino acid sequence shown in any one of SEQ ID NOs: 2 to 5, VH FWR2 having an amino acid sequence shown in any one of SEQ ID NOs: 15 to 25, VH FWR3 having an amino acid sequence shown in any one of SEQ ID NOs: 42 to 55, and VL FWR4 having an amino acid sequence shown in any one of SEQ ID NOs: 127 to 130. and VH FWR4 shown in any one of NOs: 70 to 72; More preferably, The VL comprises an amino acid sequence shown in any one of SEQ ID NOs: 151 to 167, and / or the VH comprises an amino acid sequence shown in any one of SEQ ID NOs: 132 to 149, Even more preferably, The VL comprises the amino acid sequence set forth in SEQ ID NO: 161, and the VH comprises the amino acid sequence set forth in SEQ ID NO: 143; or The VL comprises the amino acid sequence set forth in SEQ ID NO: 152, and the VH comprises the amino acid sequence set forth in SEQ ID NO: 133; or The VL comprises the amino acid sequence set forth in SEQ ID NO: 152, and the VH comprises the amino acid sequence set forth in SEQ ID NO: 146; or The VL comprises the amino acid sequence set forth in SEQ ID NO: 164, and the VH comprises the amino acid sequence set forth in SEQ ID NO: 146; or The VL comprises the amino acid sequence set forth in SEQ ID NO: 165, and the VH comprises the amino acid sequence set forth in SEQ ID NO: 146; or The VL comprises the amino acid sequence set forth in SEQ ID NO: 152, and the VH comprises the amino acid sequence set forth in SEQ ID NO: 147; or The VL comprises the amino acid sequence set forth in SEQ ID NO: 164, and the VH comprises the amino acid sequence set forth in SEQ ID NO: 147; or The VL comprises the amino acid sequence set forth in SEQ ID NO: 165, and the VH comprises the amino acid sequence set forth in SEQ ID NO: 147; or The VL comprises the amino acid sequence set forth in SEQ ID NO: 164, and the VH comprises the amino acid sequence set forth in SEQ ID NO: 133; or The VL comprises the amino acid sequence set forth in SEQ ID NO: 165, and the VH comprises the amino acid sequence set forth in SEQ ID NO: 133; or The VL comprises the amino acid sequence set forth in SEQ ID NO: 156, and the VH comprises the amino acid sequence set forth in SEQ ID NO: 138; or The VL comprises the amino acid sequence set forth in SEQ ID NO: 156, and the VH comprises the amino acid sequence set forth in SEQ ID NO: 148; or The VL comprises the amino acid sequence set forth in SEQ ID NO: 166, and the VH comprises the amino acid sequence set forth in SEQ ID NO: 148; or The VL comprises the amino acid sequence set forth in SEQ ID NO: 167, and the VH comprises the amino acid sequence set forth in SEQ ID NO: 148; or The VL comprises the amino acid sequence set forth in SEQ ID NO: 156, and the VH comprises the amino acid sequence set forth in SEQ ID NO: 149; or The VL comprises the amino acid sequence set forth in SEQ ID NO: 166, and the VH comprises the amino acid sequence set forth in SEQ ID NO: 149; or The VL comprises the amino acid sequence set forth in SEQ ID NO: 167, and the VH comprises the amino acid sequence set forth in SEQ ID NO: 149; or The VL comprises the amino acid sequence set forth in SEQ ID NO: 166, and the VH comprises the amino acid sequence set forth in SEQ ID NO: 138; or The VL comprises the amino acid sequence set forth in SEQ ID NO: 167, and the VH comprises the amino acid sequence set forth in SEQ ID NO: 138; or The VL comprises the amino acid sequence set forth in SEQ ID NO: 151, and the VH comprises the amino acid sequence set forth in SEQ ID NO: 132; or The VL comprises the amino acid sequence set forth in SEQ ID NO: 152, and the VH comprises the amino acid sequence set forth in SEQ ID NO: 134; or The VL comprises the amino acid sequence set forth in SEQ ID NO: 153, and the VH comprises the amino acid sequence set forth in SEQ ID NO: 135; or The VL comprises the amino acid sequence set forth in SEQ ID NO: 154, and the VH comprises the amino acid sequence set forth in SEQ ID NO: 136; or The VL comprises the amino acid sequence set forth in SEQ ID NO: 155, and the VH comprises the amino acid sequence set forth in SEQ ID NO: 137; or The VL comprises the amino acid sequence set forth in SEQ ID NO: 157, and the VH comprises the amino acid sequence set forth in SEQ ID NO: 139; or The VL comprises the amino acid sequence set forth in SEQ ID NO: 158, and the VH comprises the amino acid sequence set forth in SEQ ID NO: 140; or The VL comprises the amino acid sequence set forth in SEQ ID NO: 159, and the VH comprises the amino acid sequence set forth in SEQ ID NO: 141; or The VL comprises the amino acid sequence set forth in SEQ ID NO: 160, and the VH comprises the amino acid sequence set forth in SEQ ID NO: 142; or The VL comprises the amino acid sequence set forth in SEQ ID NO: 162, and the VH comprises the amino acid sequence set forth in SEQ ID NO: 144; or The anti-B7-H7 antibody or antigen-binding fragment thereof according to any one of claims 1 to 3, characterized in that the VL comprises the amino acid sequence shown in SEQ ID NO: 163, and the VH comprises the amino acid sequence shown in SEQ ID NO:

145.

5. Full-length antibody, Fab, Fab', F(ab') ２ 5. The anti-B7-H7 antibody or antigen-binding fragment thereof according to any one of claims 1 to 4, which is an Fv, preferably an scFv, a bispecific antibody, a multispecific antibody, a heavy chain antibody or a single domain antibody, or a monoclonal or polyclonal antibody produced from said antibody.

6. a full-length antibody comprising an antibody heavy chain constant region and an antibody light chain constant region, Preferably, the heavy chain constant region is selected from hIgG1, hIgG2, hIgG3, or hIgG4, and the light chain constant region is selected from a κ chain or a λ chain of a human-derived antibody; More preferably, the anti-B7-H7 antibody or antigen-binding fragment thereof according to claim 5, wherein the heavy chain constant region is hIgG1 and the light chain constant region is a κ chain of a human-derived antibody.

7. The full length antibody comprises a heavy chain and a light chain, wherein the heavy chain comprises an amino acid sequence set forth in any one of SEQ ID NOs: 169-190, and / or the light chain comprises an amino acid sequence set forth in any one of SEQ ID NOs: 192-208; Preferably, the heavy chain comprises the amino acid sequence set forth in SEQ ID NO: 186 and the light chain comprises the amino acid sequence set forth in SEQ ID NO: 202; or the heavy chain comprises the amino acid sequence set forth in SEQ ID NO: 180 and the light chain comprises the amino acid sequence set forth in SEQ ID NO: 202; or the heavy chain comprises the amino acid sequence set forth in SEQ ID NO: 184 and the light chain comprises the amino acid sequence set forth in SEQ ID NO: 193; or the heavy chain comprises the amino acid sequence set forth in SEQ ID NO: 170 and the light chain comprises the amino acid sequence set forth in SEQ ID NO: 193; or the heavy chain comprises the amino acid sequence set forth in SEQ ID NO: 187 and the light chain comprises the amino acid sequence set forth in SEQ ID NO: 193; or the heavy chain comprises the amino acid sequence set forth in SEQ ID NO: 187 and the light chain comprises the amino acid sequence set forth in SEQ ID NO: 205; or the heavy chain comprises the amino acid sequence set forth in SEQ ID NO: 187 and the light chain comprises the amino acid sequence set forth in SEQ ID NO: 206; or the heavy chain comprises the amino acid sequence set forth in SEQ ID NO: 188 and the light chain comprises the amino acid sequence set forth in SEQ ID NO: 193; or the heavy chain comprises the amino acid sequence set forth in SEQ ID NO: 188 and the light chain comprises the amino acid sequence set forth in SEQ ID NO: 205; or the heavy chain comprises the amino acid sequence set forth in SEQ ID NO: 188 and the light chain comprises the amino acid sequence set forth in SEQ ID NO: 206; or the heavy chain comprises the amino acid sequence set forth in SEQ ID NO: 184 and the light chain comprises the amino acid sequence set forth in SEQ ID NO: 205; or the heavy chain comprises the amino acid sequence set forth in SEQ ID NO: 184 and the light chain comprises the amino acid sequence set forth in SEQ ID NO: 206; or the heavy chain comprises the amino acid sequence set forth in SEQ ID NO: 185 and the light chain comprises the amino acid sequence set forth in SEQ ID NO: 197; or the heavy chain comprises the amino acid sequence set forth in SEQ ID NO: 175 and the light chain comprises the amino acid sequence set forth in SEQ ID NO: 197; or the heavy chain comprises the amino acid sequence set forth in SEQ ID NO: 189 and the light chain comprises the amino acid sequence set forth in SEQ ID NO: 197; or the heavy chain comprises the amino acid sequence set forth in SEQ ID NO: 189 and the light chain comprises the amino acid sequence set forth in SEQ ID NO: 207; or the heavy chain comprises the amino acid sequence set forth in SEQ ID NO: 189 and the light chain comprises the amino acid sequence set forth in SEQ ID NO: 208; or the heavy chain comprises the amino acid sequence set forth in SEQ ID NO: 190 and the light chain comprises the amino acid sequence set forth in SEQ ID NO: 197; or the heavy chain comprises the amino acid sequence set forth in SEQ ID NO: 190 and the light chain comprises the amino acid sequence set forth in SEQ ID NO: 207; or the heavy chain comprises the amino acid sequence set forth in SEQ ID NO: 190 and the light chain comprises the amino acid sequence set forth in SEQ ID NO: 208; or the heavy chain comprises the amino acid sequence set forth in SEQ ID NO: 185 and the light chain comprises the amino acid sequence set forth in SEQ ID NO: 207; or the heavy chain comprises the amino acid sequence set forth in SEQ ID NO: 185 and the light chain comprises the amino acid sequence set forth in SEQ ID NO: 208; or the heavy chain comprises the amino acid sequence set forth in SEQ ID NO: 169 and the light chain comprises the amino acid sequence set forth in SEQ ID NO: 192; or the heavy chain comprises the amino acid sequence set forth in SEQ ID NO: 171 and the light chain comprises the amino acid sequence set forth in SEQ ID NO: 193; or the heavy chain comprises the amino acid sequence set forth in SEQ ID NO: 172 and the light chain comprises the amino acid sequence set forth in SEQ ID NO: 194; or the heavy chain comprises the amino acid sequence set forth in SEQ ID NO: 173 and the light chain comprises the amino acid sequence set forth in SEQ ID NO: 195; or the heavy chain comprises the amino acid sequence set forth in SEQ ID NO: 174 and the light chain comprises the amino acid sequence set forth in SEQ ID NO: 196; or the heavy chain comprises the amino acid sequence set forth in SEQ ID NO: 176 and the light chain comprises the amino acid sequence set forth in SEQ ID NO: 198; or the heavy chain comprises the amino acid sequence set forth in SEQ ID NO: 177 and the light chain comprises the amino acid sequence set forth in SEQ ID NO: 199; or the heavy chain comprises the amino acid sequence set forth in SEQ ID NO: 178 and the light chain comprises the amino acid sequence set forth in SEQ ID NO: 200; or the heavy chain comprises the amino acid sequence set forth in SEQ ID NO: 179 and the light chain comprises the amino acid sequence set forth in SEQ ID NO: 201; or the heavy chain comprises the amino acid sequence set forth in SEQ ID NO: 181 and the light chain comprises the amino acid sequence set forth in SEQ ID NO: 203; or 7. The anti-B7-H7 antibody or antigen-binding fragment thereof of claim 6, wherein the heavy chain comprises the amino acid sequence shown in SEQ ID NO: 182, and the light chain comprises the amino acid sequence shown in SEQ ID NO:

204.

8. An isolated nucleic acid encoding an anti-B7-H7 antibody or antigen-binding fragment thereof according to any one of claims 1 to 7.

9. A recombinant expression vector comprising the isolated nucleic acid of claim 8, Preferably, the expression vector is a recombinant expression vector, including a eukaryotic expression vector and / or a prokaryotic expression vector.

10. A transformant comprising the recombinant expression vector according to claim 9, Preferably, the host cell of the transformant is a prokaryotic cell and / or a eukaryotic cell, the prokaryotic cell is preferably an E. coli cell, for example, a TG1, BL21 cell, and the eukaryotic cell is preferably a HEK293 cell or a CHO cell.

11. A chimeric antigen receptor comprising the anti-B7-H7 antibody or antigen-binding fragment thereof according to any one of claims 1 to 7.

12. A genetically modified cell comprising the chimeric antigen receptor of claim 11, Preferably, said genetically modified cell is a eukaryotic cell, preferably an isolated human cell, more preferably an immune cell such as a T cell or a NK cell.

13. A method for producing an anti-B7-H7 antibody or an antigen-binding fragment thereof, comprising the steps of culturing the transformant described in claim 10 and obtaining an anti-B7-H7 antibody or an antigen-binding fragment thereof from the culture.

14. 11. An antibody drug conjugate comprising an antibody portion and a conjugate portion, wherein the antibody portion comprises an anti-B7-H7 antibody or antigen-binding fragment thereof according to any one of claims 1 to 7, and the conjugate portion comprises a detectable marker, a drug, a toxin, a cytokine, a radionuclide, an enzyme, or a combination thereof, and wherein the antibody portion and the conjugate portion are conjugated via a chemical bond or a linker.

15. A pharmaceutical composition comprising an anti-B7-H7 antibody or an antigen-binding fragment thereof according to any one of claims 1 to 7, a chimeric antigen receptor according to claim 11, a genetically modified cell according to claim 12 and / or an antibody drug conjugate according to claim 14, Preferably, the pharmaceutical composition is in liquid, gaseous, solid and semi-solid dosage form, and / or the pharmaceutical composition may be administered orally, by injection, nasally, transdermally or mucosally; More preferably, The pharmaceutical composition further comprises a combination therapy, the combination therapy comprising a chemotherapeutic agent, a radiotherapeutic agent, an immunosuppressant and / or a cytotoxic drug.

16. A kit comprising an antibody or antigen-binding fragment thereof according to any one of claims 1 to 7, a chimeric antigen receptor according to claim 11, a genetically modified cell according to claim 12, an antibody drug conjugate according to claim 14 and / or a pharmaceutical composition according to claim 15, Preferably, the kit further comprises (i) a device for administering the antibody or antigen-binding fragment thereof, or chimeric antigen receptor, or genetically modified cell, or antibody drug conjugate, or pharmaceutical composition, and / or (ii) an instruction manual.

17. 13. An application of the anti-B7-H7 antibody or antigen-binding fragment thereof according to any one of claims 1 to 7, the chimeric antigen receptor according to claim 11, the genetically modified cell according to claim 12, the antibody-drug conjugate according to claim 14, the pharmaceutical composition according to claim 15 and / or the kit according to claim 16 in the manufacture of a drug for treating and / or preventing cancer, comprising: Preferably, the cancer is selected from the group consisting of lung cancer, breast cancer, gastric cancer, small intestine cancer, colon cancer, rectal cancer, pancreatic cancer, renal cancer, bladder cancer and osteosarcoma.

18. An administration device, comprising an anti-B7-H7 antibody or antigen-binding fragment thereof according to any one of claims 1 to 7, a chimeric antigen receptor according to claim 11, a genetically modified cell according to claim 12, an antibody drug conjugate according to claim 14, a pharmaceutical composition according to claim 15 and / or a kit according to claim 16, Preferably, the administration device further comprises a component for containing or administering to a subject the anti-B7-H7 antibody or antigen-binding fragment thereof, the chimeric antigen receptor, the genetically modified cell, the antibody-drug conjugate, the pharmaceutical composition and / or the kit, such as a syringe, an injection device or an implantable administration device.

19. A method for detecting B7-H7, comprising a step of detecting using an anti-B7-H7 antibody or antigen-binding fragment thereof according to any one of claims 1 to 7, a chimeric antigen receptor according to claim 11, a genetically modified cell according to claim 12, an antibody-drug conjugate according to claim 14, a pharmaceutical composition according to claim 15 and / or a kit according to claim 16, preferably wherein said detection is not for diagnostic and / or therapeutic purposes.

20. 17. A method for preventing and / or treating a disease or condition associated with B7-H7 in a subject in need thereof, the method comprising administering to the subject and detecting an anti-B7-H7 antibody or antigen-binding fragment thereof according to any one of claims 1 to 7, a chimeric antigen receptor according to claim 11, a genetically modified cell according to claim 12, an antibody drug conjugate according to claim 14, a pharmaceutical composition according to claim 15 and / or a kit according to claim 16.

21. 21. The method of claim 20, wherein the disease or condition is cancer, preferably the cancer is selected from one or more of the group consisting of lung cancer, breast cancer, gastric cancer, small intestine cancer, colon cancer, rectal cancer, pancreatic cancer, renal cancer, bladder cancer, and osteosarcoma.

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