Drug intelligence / Profile preview

454A12

Development stage
Preclinical
Modality
Monoclonal Antibodies → Antibody-Based Therapeutics
Administration
As Immunotoxin: Intravenous, As Immunotoxin: Intraperitoneal (in Animal Studies), Experimental: Intrathecal (in Animal Studies)
01

Overview

454A12 is a **murine IgG1 monoclonal antibody** targeting the **human transferrin receptor (hTfR; also known as CD71)**. It has been used primarily as a component of immunotoxins, where 454A12 is chemically conjugated to toxic agents such as recombinant ricin A chain (rRA or rRTA) or modified diphtheria toxins (CRM107), to selectively deliver cytotoxic effects to cells expressing high levels of transferrin receptor—predominantly rapidly proliferating cancer cells or abnormal proliferative cells[1][2][3]. 454A12-based immunotoxins have demonstrated potent, dose-dependent, and species-specific cytotoxicity against human cell lines derived from various cancers (e.g., medulloblastoma, glioblastoma, breast carcinoma, ovarian cancer) as well as proliferating non-cancerous cells, such as retinal pigment epithelial cells[1][2][3][4][5]. The cytotoxic mechanism relies on receptor-mediated internalization, followed by intracellular release of the toxin, resulting in inhibition of protein synthesis and induction of cell death. 454A12 immunotoxins have demonstrated efficacy **in vitro** and **in vivo** preclinical models, with pronounced cytotoxicity in malignant or proliferative tissues expressing hTfR, and minimal toxicity to low-expressing or non-human cells[1][2][3][4]. 454A12 alone (without a conjugated toxin) does not demonstrate cytotoxicity, confirming that its effect is as a targeting component for immunotoxin therapy[2].

Other names
454A12
02

Targets

TFRC (Transferrin Receptor)

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