Cd80 extracellular domain fc fusion protein dosing regimens

A technology of extracellular domain and fusion protein, which is applied in the field of administration of CD80 extracellular domain Fc fusion protein, which can solve the problems of response, relapse, and non-response of patients

Pending Publication Date: 2021-03-23
FIVE PRIME THERAPEUTICS
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

While some patients achieve long-term disease control with the aid of blocking antibodies against the PD-1 / PD-L1 and CTLA-4 axes, the majority do not respond, or respond and later relapse

Method used

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  • Cd80 extracellular domain fc fusion protein dosing regimens
  • Cd80 extracellular domain fc fusion protein dosing regimens
  • Cd80 extracellular domain fc fusion protein dosing regimens

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0085] Example 1: Cytokine Release of CD80 ECD-Fc Fusion Molecules

[0086] method

[0087] protein treatment

[0088] In the T containing RPMI 1640, 100IU penicillin (Penicillin) / 100ug / ml streptomycin (Streptomycin), 2mM L-glutamine, 100nM non-essential amino acids, 55uM 2-mercaptoethanol and 10% ultra-low-IgG fetal bovine serum Human CD80 ECD IgGl Fc fusion protein ("CD80-Fc") was bound to magnetic protein-A beads (Life Technologies) in cell proliferation medium. Binding reactions were performed at a bead concentration of three million beads per milliliter in a volume of 100 μl per well in 96-well flat bottom tissue culture plates. CD80-Fc was bound to beads in a range of concentrations: 10 μg / ml, 1 μg / ml, 0.1 μg / ml. Another set of binding reactions was also performed with the addition of 3 ng / ml OKT3-scFv. The proteins were allowed to bind for 1 hour at room temperature on a rocking platform, after which 100 μl of 20 μg / ml (final concentration 10 μg / ml) IgG1 Fc-free (...

Embodiment 2

[0097] Example 2: Effects of CD80ECD-Fc fusion molecules on CT26 tumors in vivo with different sialic acid (SA) contents in the Fc domain

[0098] An in vivo study was performed in CT26 tumors to analyze the effect of three different lots of CD80 ECD with different sialic acid (SA) content fused with wild-type human IgGl Fc. Specifically, Lot E of CD80 ECD-Fc contained 20 mol SA / mol protein, Lot D contained 15 mol SA / mol protein, and Lot A contained 5 mol SA / mol protein.

[0099] Seven-week-old female BALB / c mice were purchased from Charles River Laboratories (Hollister, CA) and acclimatized for one week prior to the start of the study. The murine colorectal cancer cell line CT26 was treated at 1.0×10 6 Cells / 200 μl / mouse were implanted subcutaneously in the right lumbar fossa of the mice. Prior to inoculation, cells were cultured in RPMI 1640 medium supplemented with 10% heat-inactivated fetal bovine serum (FBS), 2 mM L-glutamine, and passaged up to three times. cells in a...

Embodiment 3

[0105] Example 3: Effect of murine CD80 ECD-murine Fc fusion molecule on tumor growth in three different syngeneic tumor models

[0106] In vivo studies were performed using a mouse surrogate comprising the extracellular domain (ECD) of murine CD80 linked to the Fc domain of mouse IgG2a wild type (murine CD80 ECD-Fc). The effect of murine CD80ECD-Fc was compared to that of anti-CTLA4 antibody clone 9D9 (IgG2b) in three different syngeneic tumor models: CT26 colon carcinoma, MC38 colon carcinoma and B16 melanoma models.

[0107] CT26 tumor model

[0108] Seven-week-old female BALB / c mice were purchased from Charles River Laboratories (Hollister, CA) and acclimatized for one week prior to the start of the study. The murine colorectal cancer cell line CT26 was treated at 1.0×10 6 Cells / 200 μl / mouse were implanted subcutaneously in the right lumbar fossa of the mice. Prior to inoculation, cells were cultured in RPMI 1640 medium supplemented with 10% heat-inactivated fetal bovin...

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Abstract

The present disclosure provides methods of administering fusion proteins comprising the extracellular domain of human cluster of differentiation 80 (CD80) and the fragment crystallizable (Fc) domain of human immunoglobulin G 1 (IgG1) to a subject in need thereof, for example, a cancer patient.

Description

[0001] References to Sequence Listings Submitted Electronically via EFS-Web [0002] The electronically filed Sequence Listing (Name: 3986_017PC02_Seqlisting_ST25; Size: 18,864 bytes; and Date Created: August 28, 2019) is incorporated herein by reference pursuant to 37 C.F.R. §1.52(e)(5). [0003] field of invention [0004] The present application relates to a dosing regimen of a fusion protein comprising an extracellular domain (ECD) of CD80 (B7-1) and an immunoglobulin fragment crystallizable (Fc) domain for the treatment of cancer. Background technique [0005] T cell regulation involves the integration of multiple signaling pathways: signaling through the T cell receptor (TCR) complex and through co-signaling receptors, both co-stimulatory and co-inhibitory. CD80 (cluster of differentiation 80, also known as B7, B7.1, B7-1) is a well-characterized cooperative signaling ligand. It is expressed on professional antigen presenting cells (APCs) such as dendritic cells and ac...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K38/00A61P35/00C07K14/705
CPCA61K38/00C07K14/70532C07K2319/30A61P35/00A61K38/1774A61K2039/505A61K2039/545A61K9/0019A61K31/7012A61K45/06A61K2039/54C07K16/18
Inventor S·P·艾那姆达尔K·皮尔斯向红S·D·巴比
Owner FIVE PRIME THERAPEUTICS
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