Delving into the Latest Updates on Anti-TfR bispecific antibody(Alector) with Synapse

Overview

Basic Info

Drug Type

Bispecific antibody

Synonyms-

Target

TFR2 x TfR1

Mechanism

TFR2 antagonists(transferrin receptor 2 antagonists), TfR1 antagonists(Transferrin receptor protein 1 antagonists)

Therapeutic Areas

Nervous System Diseases

Active Indication

Nervous System Diseases

Inactive Indication-

Originator Organization

Alector, Inc.

Active Organization

Alector, Inc.

Inactive Organization-

Drug Highest PhasePreclinical

First Approval Date-

Regulation-

Using a doxorubicin-resistant subline (K562/ADM) of human leukaemia K562 cells (Tsuruo et al, 1986), the effect of immunoliposomes that targeted a cellular transferrin receptor (TFR) was examined by neutralization of doxorubicin (DOX) resistance. OKT9-CIL, prepared by conjugation of DOX-encapsulated liposome with an anti-TFR monoclonal antibody, OKT9 (Aisenberg and Wilkes, 1980), showed similar binding to both K562 and K562/ADM. Although an 80-fold higher sensitivity to free DOX on cell growth inhibition in K562 than in K562/ADM was found, the difference was clearly diminished after OKT9-CIL treatment through the increased sensitivity of K562/ADM. The cellular DOX level 30 min after the exposure of free DOX was 45-fold lower in K562/ADM than in K562, whereas nearly equivalent DOX levels were detected in K562 and K562/ADM after OKT9-CIL treatment. In addition, DOX in K562/ADM in the free DOX treatment was efficiently excreted by 54% within 120 min of incubation, whereas almost all DOX supplied by OKT9-CIL remained uncleared. Fluorescence microscopic observation showed that OKT9-CIL was internalized into juxtanuclear vesicles in K562/ADM cells. These results suggest that OKT9-CIL has a potency to accumulate DOX, resulting in augmentation of DOX cytotoxicity in DOX-resistant tumour cells.

100 Deals associated with Anti-TfR bispecific antibody(Alector)

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