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Anti-cd33 and Anti-cd7 combination treatment

An antigen and antibody technology, applied in the direction of drug combination, antibody, anti-receptor/cell surface antigen/cell surface determinant immunoglobulin, etc., can solve life-threatening infection, bone marrow cell consumption and other problems

Pending Publication Date: 2020-10-30
比维克特瑞斯有限公司
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Thus, as would be expected with any CD33-targeted therapy, a therapy targeting this antigen would also have numerous off-target effects on healthy cell populations, leading to a significant depletion of any myeloid cells harboring the antigen
These cells are needed for a healthy immune system, so depleting patients requires hospitalization in specialized infection control rooms, where they are highly susceptible to life-threatening infections

Method used

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  • Anti-cd33 and Anti-cd7 combination treatment
  • Anti-cd33 and Anti-cd7 combination treatment
  • Anti-cd33 and Anti-cd7 combination treatment

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0194] Example 1: Determination of IC of 5 monoclonal antibodies (individually and in combination) in Kasumi-3 cell line 50

[0195] Experimental conditions

[0196] Table A: Overview of experimental conditions tested.

[0197]

[0198] Note: CD(A)=CD33; CD(B)=CD7; CD(C)=CD13

[0199] Number of test samples

[0200] 5 antibodies or combinations * 8 concentrations * 1 cell line * 3 (triplicates) = 120

[0201] Negative control (anti-Fc linked to MMAE) * 1 concentration * 1 cell line * 3 (triplicate) = 3

[0202] 3 positive controls (primary antibodies) * 1 concentration * 1 cell line * 3 (triplicates) = 9

[0203] Control (cells without antibody treatment) * 1 cell line * 3 (triplicates) = 3

[0204] Total = 135 tests

[0205] 2.Material:

[0206] i.Kasumi-3: CRL-2725 TM

[0207] ii. RPMI-1640 medium: 30-2001 TM

[0208] iii. Fetal Bovine Serum (FBS): 30-2020 TM

[0209] iv. Dulbecco's Phosphate Buffered Saline (DPBS): Gibco TM

[0210] v. Monoclona...

Embodiment 2

[0276] Example 2: Determination of IC of 3 monoclonal antibodies (alone and in combination) in the dual antigen cell line HEL 92.1.7 50

[0277] Experimental conditions

[0278] Table C: Overview of experimental conditions tested

[0279]

[0280] Note: CD(A) = CD33; 1; CD(D) = CD56

[0281] Number of test samples

[0282] - 3 antibodies or combinations * 8 concentrations * 1 cell line * 3 (triplicates) = 72

[0283] - Negative control (anti-Fc linked to MMAE) * 1 concentration * 1 cell line * 3 (triplicates) = 3

[0284] - 2 positive controls (primary antibodies) * 1 concentration * 1 cell line * 3 (triplicates) = 6

[0285] - Control (cells not treated with antibody) * 1 cell line * 3 (triplicates) = 3

[0286] Total = 84 tests

[0287] 2.Material:

[0288] i.HEL 92.1.7: TIB-180

[0289] ii. RPMI-1640 medium: 30-2001 TM

[0290] iii. Fetal Bovine Serum (FBS): 30-2020 TM

[0291] iv. Dulbecco's Phosphate Buffered Saline (DPBS): Gibco TM

[0292] v. M...

Embodiment 3

[0347] Example 3: The second cell killing assay was repeated for Kasumi-3 using BiFab

[0348] Experiments were performed against the Kasumi-3 cell line using BiFab to repeat the second cell killing assay.

[0349] reagent

[0350]

[0351] growth medium

[0352] RPMI-1640 Medium

[0353] 10% Fetal Bovine Serum

[0354] 1% GlutaMAX Supplement

[0355] method

[0356] Harvest Kasumi-3 cells, count and divide at 2x10 4 Cells / well were seeded into 100 μl of growth medium in a 96-well plate. A 5-point dose response of WT Bifab was prepared in growth medium at 50-fold assay final concentration. 2 μl of WT Bifab titer was pipetted onto the seeded cells and each concentration was determined on triplicate wells. Cells were incubated at room temperature for 10 minutes to allow Bifab to bind. At the same time, the anti-human IgG Fab-MMAE antibody was diluted in growth medium to provide an assay final concentration of 6 nM MMAE / well, as described in the manufacturer's...

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PUM

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Abstract

This invention relates to the dual targeting of cell inhibiting agents to the cell surface receptors CD7 and CD33 in the treatment of hematological malignancy. In particular, the invention relates tocell inhibiting agents that bispecifically binds to CD33 and CD7 for use in the treatment of a CD7+CD33+ hematological malignancy. Such agents may comprise bispecific antibody drug conjugates.

Description

technical field [0001] The present invention relates to dual targeting of cytostatics to the cell surface receptors CD7 and CD33 in the treatment of hematological malignancies. Background technique [0002] Acute myeloid leukemia or acute myeloid leukemia (AML) is a heterogeneous hematological malignancy involving clonal expansion of myeloblasts in the bone marrow and peripheral blood. AML accounts for >90% of adult acute leukemia cases and remains a major aggressive disease with a fulminant clinical course. Despite advances in treatment options and current understanding of successful hematopoietic stem cell transplantation (HSCT), patients with AML still have a high mortality rate. On average, only a quarter of all adults diagnosed with AML will survive more than five years. In people over 65 years of age, the expectation is further reduced to only 12% surviving more than 5 years (www.cancerresearchuk.org). This is significantly lower than many other high-incidence ca...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07K16/28A61P35/02A61K39/395
CPCC07K16/2803A61K2039/505C07K2317/31C07K2317/55C07K2317/77C07K2319/55A61P35/02A61K35/17C07K2317/732
Inventor 蒂芙妮·简·丹尼尔斯
Owner 比维克特瑞斯有限公司