Anti-5T4 mAbs [A1](MABL-325)

MABL-325

therapeutic, ELISA

Engineer antibody

chimpanzee, Human, Cynomolgus Monkey

A1

Recombinant Antibody

This antibody binds the ectodomain regions of human 5T4 antigen which is overexpressed by a wide spectrum of cancers, including colorectal, ovarian and gastric, but with a limited normal tissue expression.

TPBG; M6P1; WAIF1; Trophoblast glycoprotein; 5T4 oncofetal antigen; 5T4 oncofetal trophoblast glycoprotein; 5T4 oncotrophoblast glycoprotein; Wnt-activated inhibitory factor 1; PF-06263507; A1mcMMAF; A1-mcMMAF; A1-mafodotin

Q13641

The original mouse antibody was generated by immunizing mice with human 5T4 antigen. Later on the CDRs of the mouse antibody were grafted onto human framework regions to generate a fully human antibody.

The epitope mapping of this antibody was done using ELISA. This antibody was used in the generation of an anti-5T4 antibody-drug conjugate (A1mcMMAF; PF 06263507) by sulfhydryl-based conjugation of the humanized A1 antibody to the tubulin inhibitor monomethylauristatin F (MMAF) via a maleimidocaproyl linker. A1mcMMAF exhibited potent in vivo antitumor activity in a variety of tumor models and induced long-term regressions for up to 100 days after the last dose. In a non-small cell lung cancer patient-derived xenograft model, A1mcMMAF treatment resulted in sustained tumor regressions and reduced TIC frequency (PMID: 23223830). Treatment with A1mcMMAF significantly improved survival without overt toxicity in mice engrafted with a 5T4-positive acute lymphoblastic leukemia cell line (PMID: 28341731). The original humanized IgG antibody A1 has a Kd of 0.9 nM against the 5T4 antigen, binds to a broad range of 5T4 expressing cell lines, and rapidly internalizes (66% internalized within 4h). As an ADC, A1mcMMAF retains similar properties to the unconjugated Ab. In vitro, A1mcMMAF exhibited receptor_x0002_density dependent cytotoxic activity against a panel of 5T4 + cell lines with an IC50 of 5 ng Ab/ml against high 5T4 expressing cells. A1mcMMAF exerts no inhibitory effect on 5T4 negative cells demonstrating it does not exert off-target activity in vitro. Against the low 5T4 expressing H1975 tumor xenograft, A1mcMMAF causes potent tumor regression in spite of its lack of in vitro inhibitory activity against this cell line (Molecular Cancer Therapeutics 10, Nov 2011, Supplement 1:A215-A215).

Sapra et al. Long-term tumor regression induced by an antibody-drug conjugate that targets 5T4, an oncofetal antigen expressed on tumor-initiating cells. Mol Cancer Ther. 2013 Jan;12(1):38-47. PMID:23223830

Describes the generation of an ADC that targets 5T4, an oncofetal antigen expressed on tumor-initiating cells (TIC), using this antibody.

100 μg Purified antibody.

1 mg/ml.

Protein A affinity purified

PBS with 0.02% Proclin 300.

Store at 4⁰C for up to 3 months. For longer storage, aliquot and store at - 20⁰C.