Advancing Cancer Immunotherapy Using Lipid Nanoparticle-Based Approaches

Pedro Henrique Dias Moura Prazeres,1,* Gabriel Henrique Costa da Silva,1,* Gabriel Vieira Azevedo,1 Natalia Jordana Alves da Silva,1 Pedro Augusto Carvalho Costa,1 Walison Nunes Da Silva,1 Anderson Oliveira Lobo,2 Pedro Pires Goulart Guimaraes1 1Department of Physiology and Biophysics, Institute of Biological Sciences, Federal University of Minas Gerais, Belo Horizonte, MG, 31270-901, Brazil; 2Department of Materials Engineering, Federal University of Piauí, Teresina, PI, 64049-550, Brazil*These authors contributed equally to this workCorrespondence: Pedro Pires Goulart Guimaraes, Department of Physiology and Biophysics, Federal University of Minas Gerais, Belo Horizonte, MG, Brazil, Email [email protected]: Cancer immunotherapy, including adoptive cell therapies, cancer vaccines, and cytokine-based therapies, have revolutionized targeted approaches in the treatment of different tumors. However, the broader application of immunotherapies, such as for engineered T cells expressing a chimeric antigen receptor (CAR-T cells), remains limited by challenges in production, systemic toxicity, and inefficient delivery, especially in solid tumors. Recent advances in nucleic acid delivery technologies, notably ionizable lipid nanoparticles (LNP), offer promising solutions to overcome these barriers. LNPs have shown potential in delivering messenger RNA (mRNA), and DNA for the generation of CAR-T cells, cancer vaccines, bispecific antibodies, and cytokine-based immunotherapies. The clinical success of LNP-based platforms in mRNA COVID-19 vaccines and interference RNA therapies for genetic disorders further validates their effectiveness in gene delivery, highlighting LNPs as versatile carriers for therapeutic nucleic acids. Furthermore, LNPs can be optimized for off-the-shelf formulations, enabling personalized treatments targeting specific patient needs. In this review, we highlight the role of LNP platforms in advancing mRNA and DNA delivery for cancer immunotherapy. We explore their potential to improve CAR-T cell production, advance cancer vaccines, and support the development of bispecific antibody- and cytokine-based therapies, ultimately paving the way for more effective, scalable, and accessible immunotherapeutic strategies.Keywords: cancer immunotherapy, adoptive cell therapy, CAR-T cells, cancer vaccines, lipid nanoparticles, gene delivery