Dimeric IgA specifically disables intracellular mutated oncodrivers

Area of Science:

• Immunotherapy
• Cancer Biology
• Molecular Medicine

Background:

• Prevailing immunotherapy dogma posits antibody therapy is limited to extracellular antigens.
• Targeting intracellular oncoproteins remains a significant challenge in cancer treatment.

Purpose of the Study:

• To investigate the potential of transcytosing dimeric-IgA antibodies for targeting intracellular oncodriver proteins.
• To demonstrate the therapeutic efficacy of antibody-mediated intracellular antigen removal in epithelial cancers.

Main Methods:

• Utilized pIgR-dependent, transcytosing dimeric-IgA antibodies.
• Administered antibody treatment to models of epithelial cancer.
• Assessed targeting, neutralization, and removal of intracellular mutated oncodriver proteins.

Main Results:

• Demonstrated successful targeting and neutralization of intracellular mutated oncodriver proteins.
• Showcased effective removal of these proteins from within epithelial cancer cells.
• Provided evidence against the limitation of antibody therapy to extracellular targets.

Conclusions:

• pIgR-dependent dimeric-IgA antibodies offer a novel strategy for intracellular cancer immunotherapy.
• This approach overcomes the traditional barrier of targeting extracellular antigens, expanding therapeutic possibilities.
• The findings pave the way for new treatments for epithelial cancers driven by intracellular mutations.