ADAM17-overexpressing breast cancer cells selectively targeted by antibody-toxin conjugates

Area of Science:

• Oncology
• Immunology
• Biochemistry

Background:

• ADAM17 (A disintegrin and metalloproteinase 17) is upregulated in breast cancer, promoting tumor growth.
• ADAM17 processes tumor-promoting proteins within the tumor microenvironment.
• Targeting ADAM17 offers a strategy against both cancer cells and their supportive environment.

Purpose of the Study:

• To evaluate the therapeutic potential of a monoclonal anti-ADAM17 antibody (A300E) for targeted cancer drug delivery.
• To determine if A300E can selectively deliver conjugated toxins to ADAM17-expressing cancer cells.

Main Methods:

• Generation of a monoclonal anti-ADAM17 antibody (A300E).
• Conjugation of toxins (doxorubicin, Pseudomonas exotoxin A) to A300E.
• Assessment of immunotoxin internalization and cytotoxicity in ADAM17-expressing cells (MDA-MB-231).

Main Results:

• The anti-ADAM17 antibody A300E was rapidly internalized by ADAM17-expressing cells.
• Doxorubicin-coupled or Pseudomonas exotoxin A-loaded A300E demonstrated potent, ADAM17-dependent killing of MDA-MB-231 breast cancer cells.
• Cytotoxicity was strictly dependent on the presence of ADAM17 on target cells.

Conclusions:

• Anti-ADAM17 monoclonal antibodies can serve as effective carriers for targeted anti-cancer drug delivery.
• This antibody-drug conjugate strategy represents a promising approach for selective cancer therapy.
• Targeting ADAM17 provides a dual benefit by addressing tumor cells and the pro-inflammatory microenvironment.