The Therapeutic Potential of Photoimmunotherapy as a Safe, Effective and Non-Toxic Treatment Option for Superficial Triple Negative Breast Cancer.

Triple-negative breast cancer (TNBC) is the most aggressive breast cancer subtype, lacking estrogen (ER), progesterone (PR), and human epidermal growth factor receptor (HER-2) expression. It disproportionately affects women of African descent and has a poor clinical prognosis attributed to its acute heterogeneity, thereby causing elevated mortality rates. Due to the lack of well-defined molecular targets in TNBC, treatment relies heavily on a trimodality approach (surgery, radiotherapy, and chemotherapy), despite growing evidence of adverse effects and disease relapses. Therefore, there is an urgency to identify targetable aberrations for more effective approaches capable of selectively detecting and killing targeted cells while sparing healthy tissues. The emergence of monoclonal antibodies (mAbs) targeting tumor-associated antigens (TAAs), which can be used as a carrier to deliver highly cytotoxic drugs, raised hopes that antibody-drug conjugates (ADCs) might solve the toxicity-therapy challenge by shifting the balance more toward beneficial therapeutic efficacy. Despite their therapeutic benefits, their clinical translation is limited by key developmental barriers, including immune-related adverse events. To address these limitations, a novel approach using antibody-photoconjugates (APCs) was developed for photoimmunotherapy (PIT) applications, whereby local exposure to near-infrared (NIR) light induces targeted phototoxic damage, culminating in apoptotic, necrotic, and immunogenic cell death (ICD) with minimal toxicities. Therefore, this review highlights the potential of PIT as an inherently safer and efficient light-dependent therapeutic option for treating TNBC. Trial Registration: NCT06449222.