The Emergence of Bispecific Antibodies: A Revolutionary Shift in Cancer Treatment

In the realm of cancer therapy, immunotherapy has emerged as a beacon of hope, surpassing traditional methods. Monoclonal antibodies, renowned for their precision in targeting specific molecules, have played a crucial role in cancer treatment. However, their effectiveness is often limited by the complexities of tumor development when focusing on a single point. Enter bispecific antibodies (bsAbs), a transformative force in tumor immunotherapy that can target multiple sites simultaneously.

The evolution of antibodies has shifted from basic forms to more intricate derivatives, with a spotlight on bsAbs of diverse shapes and sizes. BsAb technology has captured the attention of researchers, becoming a cornerstone in cancer immunotherapy. Presently, numerous preclinical and clinical trials are underway, marking the era of bsAbs in tumor immunotherapy. As of December 2021, the United States Food and Drug Administration (FDA) has granted approval for three types of bsAbs for clinical cancer treatment.

BsAbs, with their ability to simultaneously target two epitopes on tumor cells or within the tumor microenvironment, have become a pivotal element in the next generation of therapeutic antibodies. The majority of bsAbs in development function as T-cell engagers, fostering connections between immune cells, particularly cytotoxic T cells, and tumor cells, resulting in selective attacks on targeted tumor cells.

Bispecific T-cell engagers have shown promising results in clinical trials, especially in hematologic malignancies. Blinatumomab, the sole bispecific T-cell engager approved by the FDA and the European Medicines Agency, has demonstrated efficacy in treating certain forms of leukemia. Additionally, various other bispecific T-cell engagers are undergoing clinical trials, targeting a range of tumor types.

Categorized by their functional mechanisms, bsAbs include cell-cell engagers, those binding two epitopes on the same antigen, dual-functional modulators, and bsAbs in cell therapy. Innovative forms, such as those incorporating an antigen-binding Fc fragment (Fcab), offer advantages like superior tissue penetration, particularly beneficial in treating solid tumors. Fcabs also serve as a foundation for creating antibody-drug conjugates (ADCs), ensuring precise drug delivery.

While most bsAbs in clinical trials target hematologic malignancies, there is a growing need to explore their effectiveness in solid tumors, considering potential adverse effects on normal tissues. Challenges such as immune-tolerant cancer stroma, angiogenic disorders, and limited penetration of bsAb drugs contribute to the complexity of this exploration. Ongoing research in this area reflects the enthusiastic interest in expanding the applications of bsAbs in cancer treatment.

In conclusion, the research on bispecific antibodies highlights their promising prospects in innovative drug design and subsequent clinical applications for cancer treatment.