Antibodies and associates: Partners in targeted drug delivery.
Monoclonal antibodies (mAbs) are well established in the clinic due to their specificity and affinity to a diverse array of biochemical targets. More recently, mAbs are being exploited as targeting agents in modern drug delivery systems, aiming to bypass normal host tissue and to accumulate a therapeutic agent to a specific tissue or cell for enhanced pharmacology. At sizes ranging from ~10-100nm, antibody-based bioconjugates have opened up a whole new realm of clinical possibilities with several platforms emerging on the market. Antibody-drug conjugates combine the killing power of cytotoxic agents with mAb specificity and have great potential to treat cancer and beyond. Partnering a mAb with a biologic (protein/peptide, oligonucleotide (ON) or another mAb) is also gaining clinical traction. For example, many bispecific mAbs target and recruit immune effector cells to a tumor, while ON-based therapeutics against intracellular (regulatory) RNAs may be safely delivered into specific cells with mAb support. Finally, nanoparticles (NPs) offer significant drug delivery advantages including controlled release, large and diverse payloads, intracellular delivery and multi-functionality. Coupling mAbs to the surface of NPs can add further targeting capacity, and yet, therapeutic mAbs can also be encapsulated to take advantage of the above NP qualities. Here, we present an updated overview of the different aspects required for the successful development and engineering of antibody bioconjugates in current and emerging drug delivery technologies.
i3S - Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Rua Alfredo Allen 208, 4200-393 Porto, Portugal; INEB - Instituto de Engenharia Biomédica, Universidade do Porto, Rua Alfredo Allen 208, 4200-393 Porto, Portugal; Ipatimup - Instituto de Patologia e Imunologia Molecular da Universidade do Porto, Rua Alfredo Allen 208, 4200-393 Porto, Portugal; ICBAS - Instituto de Ciências Biomédicas Abel Salazar, Universidade do Porto, Rua de Jorge Viterbo Ferreira 228, 4050-313 Porto, Portugal.
Patrick J
PJ
Kennedy
i3S - Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Rua Alfredo Allen 208, 4200-393 Porto, Portugal; Ipatimup - Instituto de Patologia e Imunologia Molecular da Universidade do Porto, Rua Alfredo Allen 208, 4200-393 Porto, Portugal.
Carla
C
Oliveira
i3S - Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Rua Alfredo Allen 208, 4200-393 Porto, Portugal; INEB - Instituto de Engenharia Biomédica, Universidade do Porto, Rua Alfredo Allen 208, 4200-393 Porto, Portugal; ICBAS - Instituto de Ciências Biomédicas Abel Salazar, Universidade do Porto, Rua de Jorge Viterbo Ferreira 228, 4050-313 Porto, Portugal; FEUP - Faculdade de Engenharia da Universidade do Porto, Departmento de Engenharia Metalúrgica e de Materiais, Rua Dr. Roberto Frias, 4200-465 Porto, Portugal.
Pedro L
PL
Granja
i3S - Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Rua Alfredo Allen 208, 4200-393 Porto, Portugal; INEB - Instituto de Engenharia Biomédica, Universidade do Porto, Rua Alfredo Allen 208, 4200-393 Porto, Portugal; CESPU - Instituto de Investigação e Formação Avançada em Ciências e Tecnologias da Saúde, Instituto Universitário de Ciências da Saúde, Rua Central de Gandra, 1317, 4585-116 Gandra, Portugal. Electronic address: bruno.sarmento@ineb.up.pt.
Bruno
B
Sarmento
D000818:Animals; D000906:Antibodies / Q000008:administration & dosage* / Q000627:therapeutic use; D001688:Biological Products / Q000008:administration & dosage / Q000627:therapeutic use; D001709:Biotechnology; D016503:Drug Delivery Systems; D006801:Humans; D018796:Immunoconjugates / Q000008:administration & dosage / Q000627:therapeutic use; D053758:Nanoparticles / Q000008:administration & dosage / Q000627:therapeutic use
D000906:Antibodies; D001688:Biological Products; D018796:Immunoconjugates
Antibody-drug conjugate; Bispecific antibody; Intracellular antibody; Monoclonal antibody; Nanoparticle; Oligonucleotides