In search of the “Magic Bullet” Overcoming the limitations of traditional antibody treatment with gene therapy

Abstract

Traditional monoclonal antibody (mAb) therapies have proven successful in treating a wide range of diseases such as cancer, autoimmune disorders, and infectious diseases. However, traditional mAb therapy faces significant limitations, such as high production costs, frequent dosing, and fluctuating pharmacokinetics. Antibody gene therapy (AGT) is an innovative approach that offers an alternative to traditional therapy. AGT overcomes these challenges by delivering genetic material encoding therapeutic antibodies directly into patient cells, resulting in long-term, stable, and potentially self-sustained antibody production. This thesis presents a review of the mechanisms involved in AGT, focusing on the key strategies for in vivo and ex vivo gene delivery, including viral and non-viral vectors, and exploring the use of CRISPR/Cas9 gene-editing technology for precise integration of antibody genes.

The thesis discusses AGT in detail, where it discusses advancements in AGT. Particularly advancements in the engineering of B-cells and plasma cells, which have been shown to produce antibodies over extended periods in preclinical models. Non-B-cell approaches are explored as well, demonstrating the use of AGT beyond the immune system. The thesis highlights AGT’s potential to address the limitations of traditional antibody therapies. Ultimately, AGT offers the potential for single-dose, long-term treatments that could reduce the burden on patients and treatment costs. However, challenges such as immune responses to vectors, the risk of off-target effects with CRISPR/Cas9, and the need for the optimization of vector systems still need to be solved before AGT can be implemented in human medicine.