Therapeutic antibodies: precision medicine for multiple diseases

The potentiality of Monoclonal Antibodies (mAbs)

From its discovery, the humoral immune system has always been considered as a fundamental weapon for our health able to defend the body against antigens derived from microorganisms, viruses and everything which is considered alien to the body, as antigens expressed on cancer cells. Due to this, antibodies are among the most interesting and favourable tools used in medicine and pharmaceuticals. Unlike the natural immune response, which generates a polyclonal antibody response, monoclonal antibodies (mAbs) can be engineered and modified to precision. Their ability to target specific antigens makes them highly effective for therapeutic use.

Technological advancements have significantly improved the development of mAbs. Methods such as immunoglobulin transgenic mice, single B cell receptor (BCR) DNA sequencing, and phage display have helped the identification and the cloning of the desirable antibody.

Next-Generation Antibodies: Beyond the Basics

In recent years, new antibody formats and fragments are considered for the pharmaceutical and diagnostic development. In the past, the most useful formats were single-chain fragment variable (scFv) format, which consists of VL and VL segment jointed by a linker, and fragment antigen binding (Fab) format, in which VH-CH1 and VL-CL are connected by a non-covalent binding.

Now, thanks to the advance in molecular biology, scientists have developed new formats with unique capabilities, including:

Polyspecific (multispecific) antibodies: contain different binding sites capable of targeting distinct antigens
Catalytic antibodies: can hydrolyze substances
Minibody: has the same structure of scFv plus the late portion of the constant region of the heavy chain (CH3) to allow the dimerization
Nanobodies: a single domain antibody (VHH), which consisted of two H chains, each with a single variable domain
Fc-engineered antibodies: allow to choose the right IgG effector activities
Antibody-drug conjugates: allow targeted-delivery of small molecule pharmaceutical

Therapeutic use of mAbs

The growing potential of monoclonal antibodies is reshaping the treatment landscape across multiple medical fields:

Cardiovascular diseases: mAbs can address different aspects such as lipid metabolism, inflammation and blood clotting management.
Respiratory diseases: mAbs can bind specific targets of the immune system to decrease symptoms and allow a better management of the disease progression.
Autoimmune diseases: mAbs can target specific molecules involved in the diseases, acting directly by inducing apoptosis or indirectly by ADCC. Among them, the most autoimmune diseases treated with monoclonal antibodies are: rheumatoid arthritis, systemic lupus erythematosus, diabetes
Oncology: mAbs can block cancer cells directly or promote the induction of long-lasting immunological response connecting malignant cells and immune system effector cells or complement system. Moreover, some of mAbs used for these purposes function as activators of immunological checkpoints.
Viral diseases: neutralizing mAbs are able to block the viral infection
Bacterial diseases: mAbs can target bacterial endotoxin or opsonize pathogens to block the infection
Fungal and parasitic diseases: mAbs can be useful in these diseases by their different mechanisms of action (direct or indirect). Due to the complexity of these organisms, few species of fungi and protozoa are studied for an effective treatment by antibodies.

A Booming Market with No Signs of Slowing Down

Since the FDA approved the first monoclonal antibody in 1986, the field has experienced exponential growth. Today, monoclonal antibodies dominate the biopharmaceutical market, with new therapies continuously emerging.

Sources: https://link.springer.com/article/10.1186/s43556-024-00210-1