Advanced therapy medicinal products for local treatment using new delivery methods

Over the past years, an increasing number of advanced therapy medicinal products (ATMPs) have received marketing authorization, including gene therapy, somatic cell therapy, and tissue-engineered medicines, fostering development in this field. ATMPs utilise delivery methods effectively introducing recombinant nucleic acids into target cells and tissues to treat a patient's disease or condition by transferring genetic sequences. In therapeutic settings, it utilizes non-immunogenic vectors with cell- and tissue-specificity that can provide adequate transgene expression to achieve the desired effect. In addition, autologous cells, such as T cells, can be modified ex vivo to target epitope-expressing tissues, e.g. in cancer and rheumatoid arthritis therapy. Overexpression of specific genes or inhibitory molecules can effectively influence cellular regulation. Systemic gene therapy often results in lower specificity, as it can affect unintended tissues and cells, leading to off-target effects and potential side effects such as hepatotoxicity. Additionally, systemic approaches regularly require higher doses to achieve efficacy in the desired tissue or organ, increasing the likelihood of adverse reactions. In contrast, local cell and gene therapy might allow precise delivery to the target area, minimizing risks and improving therapeutic outcomes. This review summarises current knowledge of different delivery methods for ATMPs and the materials used to implement them, as the choice of application method depends on the disease, the target tissue, and the properties of the substance. It discusses the advantages and disadvantages of various delivery possibilities across multiple therapy applications. Finally, current clinical studies and perspectives on localized therapy approaches will be summarised.