Low Antibody Dosing in Cancer Therapy: Targeted Cytotoxicity Combined with Anti-Tumour Immunostimulation

Area of Science:

• Oncology
• Immunology
• Pharmacology

Background:

• Tumour cells overexpress growth factor receptors and immunosuppressive molecules, aiding proliferation and immune evasion.
• This co-expression creates a unique vulnerability for targeted therapies.
• Current therapies may lack specificity, affecting both normal and malignant cells.

Purpose of the Study:

• To propose a novel therapeutic strategy combining monoclonal antibodies (mAbs) against two distinct tumour antigens.
• To achieve selective tumour cell destruction by targeting co-expressed antigens at sub-cytotoxic doses.
• To enhance anti-tumour immune responses and facilitate clinical translation.

Main Methods:

• Employing a combination of monoclonal antibodies (mAbs) targeting two distinct antigens (Ags).
• Utilizing sub-cytotoxic doses to achieve a threshold cytotoxic density of immune complexes selectively on malignant cells.
• Targeting growth factor receptors (e.g., EGFR, HER2, VEGFR2) and immunosuppressive molecules (e.g., PD-L1).

Main Results:

• Selective immune complex formation on malignant cells co-expressing both target antigens.
• Sparing of normal cells expressing only one of the target antigens.
• Expected enhancement of neoantigen (NeoAg) presentation and stimulation of anti-tumour immune responses via PD-1/PD-L1 blockade.

Conclusions:

• This dual-mAb strategy offers selective tumour destruction while sparing normal tissues.
• The approach has the potential to enhance anti-tumour immunity.
• Utilizing clinically approved therapeutic mAbs could expedite clinical application.