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T cell depletion therapy

A cell and cytotoxin technology, applied in chemical instruments and methods, medical raw materials derived from mammals, allergic diseases, etc., can solve problems such as patient illness

Pending Publication Date: 2022-03-18
美真达治疗公司
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Although T cells are an important part of the immune system, abnormal T cell activity can lead to disease in patients

Method used

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Examples

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preparation example Construction

[0738] Preparation of antibody-drug conjugates

[0739] Among the ADCs, the antibody or antigen binding fragment thereof is conjugated to one or more cytotoxic drug moieties (D), such as one or more cytotoxic drug moieties (D), as disclosed herein. 20 drug parts. The ADCs of the present disclosure can be prepared by a variety of pathways, and an organic chemical reaction, conditions, and reagents known to those skilled in the art, including: (1) antibody or antigen-binding fragment reactive substituent reaction formation with a divalent ligation reagent As described above, the AB-ZL described above is then reacted with the drug portion D; or the reactive substitution of the drug portion reacts with the divalent joint reagent to form a DLZ, then the antibody as described above or its antigen binding fragment. The reactive substituent reaction has formed an ADC of formula DLZ-AB, such as AM-ZL-AB. Further methods of preparing ADCs are described herein.

[0740] In another aspect, th...

Embodiment 1

[0777] Example 1: In vitro binding analysis of anti-CD2 antibody.

[0778] In order to determine the binding features of anti-CD2 antibody RPA-2.10 migg1 and AB1 HIGG1, at 25 degrees Celsius (BLI) using the PALLTEBIO OCTET RED96 using the PALLTEBIO OCTET RED96 in 1 xpbs added 0.1% W / V borey albumin. Antibody binding studies. The designated purified human (AB1-HIGG1) antibody was immobilized in an anti-human FC biosensor (AHC; PALLTEBIO 18-5063) or a mouse Fc biosensor (AMQ; PallFortebio 18-5090) Extracellular and EtOAc EtOAc EtOAc EtOAc EtOAc. Apparent single price affinity (K D ), Apparent binding rate (k ON ) And apparent dissociation rate (K DIS The partial fully fitted to the 1: 1 binding model is determined, such as the calculation of each IgG and purified human CD2 extraordinary domain, as shown in Table 3, is shown in Table 3.

[0779] Further characterization of anti-CD2 antibodies is provided in Examples 2 to 6.

[0780] table 3: Combined kinetics of designated IgG and...

Embodiment 2

[0782] Example 2: In vitro cell line combination analysis of anti-CD2 antibody

[0783] Molt-4 cells (i.e.. G4 or LT2) was stained at 4 ° C for 2 hours. A constant amount of secondary anti-mouse AF488 stain was added at 4 ° C for 30 minutes. After washing, the board operates on a streaming cytometry and determines the binding of the specified antibody (and negative control, MIGG1) based on geometric average fluorescence intensity in the AF488 channel. figure 1 The results of these assays are provided.

[0784] Such as figure 1 As shown, the mouse anti-CD2 antibody RPA-2.10, TS1 / 8, BH1, UMCD2, 1E7E8.G4 and LT2 combined with human T lymphobocytes (ie Molt-4 cells), EC 50 = 160 pm (RPA-2.10), 125PM (TS1 / 8), 639PM (BH1), 151PM (UMCD2), 134PM (1E7E8) and 60PM (LT2).

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Abstract

Provided herein are methods of depleting T cells for therapeutic use comprising administering an anti-CD2 or anti-CD5 antibody drug conjugate (ADC) for therapy. Anti-CD2 ADCs or anti-CD5 ADCs are provided for use as agents for the treatment of stem cell disorders, cancer or autoimmune diseases, as well as other hematological and proliferative diseases. The described compositions and methods can be used to deplete a population of CD2 + or CD5 + cells, such as CD2 + or CD5 + cancer cells or CD2 + or CD5 + immune cells, and can also be used to prepare for hematopoietic stem cell transplantation or solid organ transplantation for a patient.

Description

[0001] Application [0002] The present application claims priority to US Provisional Application No. 62 / 857,744, filed on June 5, 2019, which is incorporated herein by reference. [0003] Sequence list [0004] The present application contains a sequence list that has been submitted by EFS-Web in ASCII format, and is incorporated herein by reference in its entirety. The ASCII copy was founded on June 3, 2020, named M103034_2170WO_SL.TXT, size of 91,817 bytes. [0005] Inventory background [0006] T cells are a type of lymphocyte developed in the thymus and an important role in the immune response. Although T cells are an important part of an immune system, abnormal T cell activity can lead to patients with patients. For example, graft anti-main disease (GVHD) is mainly caused by donor T cells in grafts, resulting in host tissue damage. Other examples of abnormal T cell activity caused by diseases include T cell-related cancers, such as T cell lymphoma. Targeting T cells Therapy ...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K35/17A61K39/395A61P35/02
CPCA61P35/02C07K16/2806C07K2317/92C07K2317/73C07K16/2896A61K2039/505A61K47/6831A61K47/6849A61K38/07A61K38/12A61K38/08A61K47/6867A61P37/06
Inventor A.博伊塔诺M.库克S.麦克唐纳J.L.普罗克特
Owner 美真达治疗公司
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