Monoclonal Antibodies Against Chitinase 3-like-1 (Chi3l1) for Therapeutic and Diagnostic Use

Description:

Researchers at UTHealth have unveiled a critical role of Chi3l1 in hepatic platelet recruitment during acetaminophen (APAP)-induced liver injury (AILI) using murine models of AILI and concanavalin A (Con A)-induced hepatitis. Significantly, they have developed anti-Chi3l1 monoclonal antibodies and demonstrated the feasibility of targeting CHI3L1 by neutralizing such monoclonal antibodies for the treatment of AILI and perhaps other acute liver injury conditions, as well as the potential to treat many solid tumor types, including hepatocellular carcinoma (HCC) and metastatic breast cancer.

Background

Acetaminophen (APAP) overdose triggers blood clotting and inflammation and is the leading cause of drug-induced acute liver failure (ALF) in many developed countries. In patients with APAP overdose, hepatic platelet accumulation critically contributes to AILI.

Discovery

Researchers at UTHealth have generated anti-Chi3l1 monoclonal antibodies and demonstrated the utilities of those antibodies for inhibition of solid tumor growth (hepatocellular carcinoma and metastatic breast cancer) and treatment of acute liver injury and hepatocellular carcinoma.

Benefits/Technology Advantages

The anti-Chi3l1 antibodies can prevent hepatic platelet accumulation by neutralizing Chi3l1, which plays a critical role in exacerbating the liver injury, and can be the new drug targets for AILI and perhaps other acute liver injury conditions
Targeting Chi3l1 by monoclonal antibodies in solid tumors is a novel strategy and has the potential to become the first-in-class therapeutics for the treatment of many solid tumor types, including HCC and metastatic breast cancer
Targeting Chi3l1 produced by tumor-associated macrophages could be promising immunotherapy targeting the tumor microenvironment

Potential Applications

Use as diagnostic or therapeutic agents for AILI
Production of diagnostic kits for use in detecting and diagnosing cancer, as well as for cancer therapies
Potential immunotherapy targeting the tumor microenvironment