Therapeutic Antibodies in Medicine

Abstract

Antibody engineering has developed into a wide-reaching field, impacting a multitude of industries, most notably healthcare and diagnostics. The seminal work on developing the first monoclonal antibody four decades ago has witnessed exponential growth in the last 10-15 years, where regulators have approved monoclonal antibodies as therapeutics and for several diagnostic applications, including the remarkable attention it garnered during the pandemic. In recent years, antibodies have become the fastest-growing class of biological drugs approved for the treatment of a wide range of diseases, from cancer to autoimmune conditions. This review discusses the field of therapeutic antibodies as it stands today. It summarizes and outlines the clinical relevance and application of therapeutic antibodies in treating a landscape of diseases in different disciplines of medicine. It discusses the nomenclature, various approaches to antibody therapies, and the evolution of antibody therapeutics. It also discusses the risk profile and adverse immune reactions associated with the antibodies and sheds light on future applications and perspectives in antibody drug discovery.

Keywords: drug development; drug discovery; medicine; protein engineering; therapeutic antibodies.

Figure 1

Overview of monoclonal antibodies and their variants with old and new naming conventions. (a) shows murine, human, chimeric, and humanized antibodies. The chimeric antibody has a variable region of murine origin (light blue) and a constant region sourced from a human antibody (coral orange). The humanized antibody is mostly human except for the complementarity-determining regions (CDRs, light blue lines) or hypervariable regions, which are of murine origin. The old and new nomenclature for antibodies are mentioned beneath each picture. The murine and human antibodies are unaltered, so they contain the stem “tug” compared to the chimeric and humanized antibodies, which carry the stem “bart”. The biosimilars have a random 4-letter suffix. (b) shows the variants of antibodies available, viz. antibody-drug conjugate (ADC), bispecific antibodies, fragment antibodies (with variable (VL + VH) and constant domain 1 (CH1 and CL) from both heavy and light chains), and single-chain fragment antibodies like single-chain fragment variable (scFv − VH + VL) and variable heavy domain (VHH). This figure is based on a paper by Wang et al. (2022) [17].

Figure 2

Overview of monoclonal antibody therapies. There are three main categories. The first category utilizes naked antibody and kills the target cell by antibody-dependent cell-mediated cytotoxicity (ADCC) and complement-dependent cytotoxicity (CDC). The second category comprises immunoconjugates where an antibody is linked to a radionuclide (radioimmunoconjugate), drug (antibody-drug conjugate), enzyme (antibody-directed enzyme prodrug therapy, ADEPT), or liposome (immunoliposome). The third category utilizes a multistep targeting approach where the antibodies are engineered to be specific either to the chimeric T-cell signaling domain/receptor (CAR-T) or T-cell marker (bispecific antibodies), along with specificity towards target cell for enhanced effector function (adapted from Carter 2001 [18], and Lu et al. 2020 [19]).

Figure 3

Number of antibody therapeutics in cancer and non-cancer categories that were granted first approval either in the United States (US) or the European Union (EU) from 1997–2021. This graph is adapted from The Antibody Society. Therapeutic monoclonal antibodies approved or under review in the EU or US. [47] www.antibodysociety.org/resources/approved-antibodies, accessed on 30 June 2023.