Maad Rayan Publishing Company Biomedical Research Bulletin 2980-9924 2 2 2024 06 28 Enhancing Antibody Uptake: Strategies for Improved Immunotherapy Efficacy 75 78 10.34172/biomedrb.2024.12 EN Shiva Alipour https://orcid.org/0000-0002-4596-2508 Rozita Abolhasan Leili Aghebati-Maleki https://orcid.org/0000-0002-0044-5961 REVIEW 10.34172/biomedrb.2024.12 2024 05 29 2024 06 09 Antibodies play a starring role in immunotherapy for numerous tumors and neurodegenerative disorders such as Alzheimer’s disease (AD). Nevertheless, low uptake of antibodies, especially monoclonal antibody (mAb) therapy, in solid tumors limits the effectiveness of these therapeutics due to tumor-specific physiological features. This review scrutinizes the significance of antibody uptake and discusses methods to improve it because enhancing their uptake is crucial for better therapeutic efficacy. Different factors, including antigen expression, antibody-antigen affinity, receptors, vascular permeability, and tumor size, influence antibody uptake. Hence, several strategies have been investigated to overcome these obstacles, including magnetic resonance-guided focused ultrasound (MR-FUS) treatment, bivalent brain shuttles, nanomaterials such as zeolite nanocrystals, and fibrosis pathway antagonists such as relaxin-2 by reducing extracellular matrix (ECM) accumulation and improving antibody transport in solid tumors. Furthermore, cholesterol-sequestering agents and hyaluronidase have been examined to enhance antibody uptake via controlling receptor trafficking and removing hyaluronan barriers. Combination therapies, including molecular and external radiotherapy or mAb immunotherapy and vasoactive immunoconjugates, have demonstrated augmented uptake. In conclusion, increasing antibody uptake is essential for boosting immunotherapy’s effectiveness in various disorders, and various strategies lead to encouraging outcomes to get beyond the drawbacks of limited antibody uptake. Gaining knowledge about them and putting these promising tactics into practice can help improve the results of cancer treatment.