Quantum leap of monoclonal antibody (mAb) discovery and development in the COVID-19 era

Abstract

In recent years the global market for monoclonal antibodies (mAbs) became a multi-billion-dollar business. This success is mainly driven by treatments in the oncology and autoimmune space. Instead, development of effective mAbs against infectious diseases has been lagging behind. For years the high production cost and limited efficacy have blocked broader application of mAbs in the infectious disease space, which instead has been dominated for almost a century by effective and cheap antibiotics and vaccines. Only very few mAbs against RSV, anthrax, Clostridium difficile or rabies have reached the market. This is about to change. The development of urgently needed and highly effective mAbs as preventive and therapeutic treatments against a variety of pathogens is gaining traction. Vast advances in mAb isolation, engineering and production have entirely shifted the cost-efficacy balance. MAbs against devastating diseases like Ebola, HIV and other complex pathogens are now within reach. This trend is further accelerated by ongoing or imminent health crises like COVID-19 and antimicrobial resistance (AMR), where antibodies could be the last resort. In this review we will retrace the history of antibodies from the times of serum therapy to modern mAbs and lay out how the current run for effective treatments against COVID-19 will lead to a quantum leap in scientific, technological and health care system innovation around mAb treatments for infectious diseases.

Neutralizing monoclonal antibodies for treatment of COVID-19

“…Furthermore, a high titre of neutralizing antibodies — which current evidence indicates is necessary for the efficacy of CPT — is inherent with neutralizing mAbs. As of March 2021, at least 20 neutralizing mAb therapies were being tested in late-stage clinical trials or had already been approved for use in nine infectious diseases, including RSV infection and Ebola 29 , 30 ( ClinicalTrials.gov ).…”

Identification of Human SARS-CoV-2 Monoclonal Antibodies from Convalescent Patients Using EBV Immortalization

“…Modified techniques for isolating memory and/or antigen-specific B cells, improving EBV infection rate, and expansion of single clones have been later developed and optimized, most prominently by Antonio Lanzavecchia’s group. Indeed, human mAbs against a wide variety of infectious agents, including SARS-CoV, influenza virus, Ebola, HIV, etc., have been relatively easily identified and isolated [ 1 , 2 , 3 , 4 , 18 , 19 , 20 ].…”

CrossTORC and WNTegration in Disease: Focus on Lymphangioleiomyomatosis

“…Quantum advances in mAb discovery and development have occurred before and during the Corona Virus Disease (COVID-19) era [ 84 ]. These include improvements and decreases in costs of production, novel advances in combination antibody therapies, and DNA-directed [ 85 ] and mRNA-directed antibody production [ 86 ].…”