The Next Generation Antibody Therapeutics

Next Generation Antibody Therapeutics

Antibodies are becoming more and more known and dominant in biopharmaceuticals ever since the introduction of the first therapeutic monoclonal antibodies in the 80s. Due to increased research in the development of medicine, technological advancements, investments in the health care system, and demand for biological substances for chronic diseases, more focus is now being given to the development of several noble antibody therapeutics formats, which is based on the m=dification of the conventional immunoglobulin G (IgG). The intensity of interest in this aspect results in an additional inventory of therapeutics molecules in the next-generation antibody therapeutics.

Characteristics of antibody therapeutics

There are several features of the conventional immunoglobulin G (IgG) format which has sustained interest in the therapeutic modality, and the characteristics of antibody therapeutics are

  • Antibodies show an intense binding specificity, and it limits the off-target effects. This, in turn, improves the clinical safety of the profile.
  • Full human therapeutic antibodies and humanise indicate low intrinsic toxic immunogenicity due to similar molecules present at substantial concentrations in the circulatory system.
  • Therapeutic antibodies can enlist the function of the immune cell to antigen expression. This is done through fragment crystallizable (Fc), and the functions of the effector may be made to fit into the therapeutic target 
  • There is a long half-life due to recycling through the neonatal Fc Receptor (FcRn).

Fragments of therapeutic antibodies

The competition for antibodies in antibody therapeutics keeps expanding and becoming intense. Bispecific antibodies such as the BPCAM antibody are among the next-generation antibody therapeutics capable of binding two separate target antigens using the two components of immunoglobulin G (IgG) molecules. They can be used for any form of therapeutic needs. 

Out of the existing antibodies, three Fab therapeutic fragments have been approved by FDA. These three fragments of therapeutic antibodies are ReoPro® (abciximab) – an anti-gpIIb/IIIa Fab fragment meant to prevent blood clots in angioplasty.

Lucentis® (ranibizumab) is an anti-VEGF Fab fragment indicating the treatment of the wet form of age-related macular degeneration.

Cimzia® (certolizumab pegol) – this antibody is a PEGylated anti-TNFα Fab fragment used for Crohn’s disease and rheumatoid arthritis. The Fab fragments are the simplest form of antibody- p53 antibody, a derived molecule formed by proteolytic digestion. An improvement in the development of antibodies expansion in structure and functions of immunoglobulin G gave space for the next generation antibodies fragments, which are in clinical testing.

Therapeutics antibodies mechanisms of action

The potency that therapeutic antibodies have emanated from several functions of natural antibodies. They entail neutralisation, antibody-dependent cell-mediated cytotoxic (ADCC), complement-dependent cytotoxic (CDC), and medical substance delivery carrier antibody.

Neutralisation: in blocking the pathophysiological functions of the target molecules, several therapeutic antibodies use this neutralisation to do so. This makes the antibodies bind with the ligand or receptor expressed on the cell’s surface and also blocks the target signalling pathways. This then leads to the loss of cellular activities, inhibited proliferation, activation of pro-apoptotic programs, or re-sensitization of cells to a cytotoxic agent.

Antibody-dependent cell-mediated cytotoxic (ADCC): when the FV binding domain of antibodies gets attached to particular antigens expressed on the target cells’ surface, the ADCC becomes triggered. With this, the antibody will be able to recruit immune effector cells. 

Complement-dependent cytotoxic (CDC): in this, the complex C1 antibody binds to the antigen complex, which then activates streams of complement proteins. This process causes complexity to form, which attacks the membrane and results in the lysis of the target cells. The interactions involve elements of the host immune system. This therapeutic is among those that are being developed to treat cancer.

Medical substance delivery carrier antibody: when an antibody is conjugated with radioisotopes, toxins, cytokines, it can be used and applied as a medical substance delivery carrier. The conjugate of this antibody is more beneficial than the conventional medical substance because of the direct delivery of the cytotoxic agents at a higher local concentration to tumour tissues without causing damage to the cells.

Future trends of antibody therapeutics 

The techniques employed in developing antibodies have taken a more advanced approach which is bringing in progress. As a result, it is now possible for researchers and scientists alike to create more antibodies using a diverse selection of functions. Antibodies like the Tim 3 antibody, which has efficient, long-lasting neutralising effects, cytotoxicity agents with low molecule expressions, or bispecific antibodies capable of detecting two separate molecules which can induce new biological responses, are used.

The advance in therapeutic antibodies of the next generation with the new target molecules gives more knowledge on the possibility of the new therapies. Understanding the biological functions of target molecules and the biological responses in line with the modified functions of the antibody is necessary to know how it works for therapeutic antibody results.

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