Production of a High-affinity Monoclonal Antibody Reactive with Folate Receptors Alpha and Beta

Area of Science:

• Immunology
• Oncology
• Molecular Biology

Background:

• Folate receptors alpha (FRα) and beta (FRβ) are cell surface glycoproteins that bind folate.
• FRα is highly expressed in cancer cells, making it a target for tumor-specific therapies.
• FRβ is expressed on tumor-associated macrophages that can promote tumor growth.

Purpose of the Study:

• To develop a single monoclonal antibody (MAb) capable of targeting both FRα and FRβ.
• To evaluate the therapeutic potential of a dual-targeting anti-FRαβ MAb for cancer treatment.

Main Methods:

• Development of a novel monoclonal antibody (MAb) against both FRα and FRβ.
• Immunohistochemical staining of various human and animal tissues, including cancer cells and macrophages.
• Surface plasmon resonance (SPR) to assess binding affinity to soluble FRα and FRβ.
• In vitro functional assays including complement-dependent cytotoxicity (CDC), antibody-dependent cellular cytotoxicity (ADCC), and antibody-dependent cellular phagocytosis (ADCP).

Main Results:

• The developed MAb, anti-FRαβ, specifically stained FRα-expressing cancer cells and FRβ-expressing macrophages in various cancer types and tissues.
• SPR analysis confirmed high-affinity binding of the anti-FRαβ MAb to both soluble FRα and FRβ proteins.
• In vitro studies demonstrated that the anti-FRαβ MAb effectively mediates CDC, ADCC, and ADCP against cell lines expressing FRα or FRβ.

Conclusions:

• The novel anti-FRαβ MAb is a promising therapeutic candidate for cancers.
• This MAb can simultaneously target cancer cells and tumor-promoting macrophages, offering a potentially more potent therapeutic strategy.
• The dual-targeting approach may overcome limitations of therapies targeting only FRα or FRβ individually.