Monoclonal antibodies are important medicines used in the treatment of a wide variety of conditions – from rheumatoid arthritis to cancer. Here, we review the pharmacology of anticancer monoclonal antibodies – the details you need to know.

What are monoclonal antibodies? As their name suggests, these drugs are synthetic antibodies that have been engineered to restore, enhance, or replicate the body’s immunological response to certain attacks – such as from cancer cells.

Monoclonal antibodies are far more specific, in that they are designed to target cancer cells rather than healthy cells. This can, and is, achieved because the target antigens are more concentrated on cancer cells.

There are four types of monoclonal antibodies:

  • Murine monoclonal antibodies
  • Chimeric monoclonal antibodies
  • Humanized monoclonal antibodies
  • Human monoclonal antibodies

The first approved monoclonal antibody was muromonab produced from murine monoclonal antibodies. Scientists produced murine antibodies by vaccinating mice or hamsters with target antigens, stimulating B cells to produce antibodies against it. These B cells are present in the spleen, so these cells were removed and fused with immortal B lymphocyte tumor cells.

Fusion was needed because B cells cannot divide on their own, while tumor cells replicate rapidly. The fused cell is called a hybridoma cell, which reproduces fast and produces antibodies against a particular antigen. The antibodies produced by these hybrid cells showed severe side effects which limited their use. This occurred because the human body is trained to attack anything it recognizes as foreign.

Then chimeric monoclonal antibodies were produced, first approved in 1994. They had the same murine hybridoma technique for the generation of antigen-specific mouse antibodies, but the constant regions were replaced with human antibody. This technique helped minimize adverse effects because the number of foreign epitopes introduced to the patient were reduced.

Then, humanized monoclonal antibodies were produced in which all the regions of the mouse’s antibody were replaced by human counterparts – excluding the complementarily-determining regions. The latest generation of monoclonal antibodies are fully humanized. They are produced by two methods.

First, by genetically altering the mouse’s immune system to carry human antibody genes. Secondly, by phage display techniques. This involves the insertion of a genomic library of complementarily determining regions into the bacteriophage virus, which expresses them. Then, these regions are grafted onto human scaffold forming a human monoclonal antibody. They have the least adverse effects of all.

Anticancer Monoclonal Antibodies

Here, we explore many of the most widely used anticancer monoclonal antibodies. This is not intended to be a complete list, but does specify some of the most important medicines, their indications and adverse effects.

Humanized monoclonal antibodies.
They have a suffix -zumab, mostly derived from a human source apart from the part that binds to the target.
Monoclonal antibodiesMechanism of actionIndicationsAdverse effectsOther comments
BevacizumabIt binds to vascular endothelial growth factor (VEGF) and inhibits it from binding to the receptors, mostly on endothelial cells.
Antiangiogenic drug.
Metastatic colorectal cancer
Non -small cell lung carcinoma
Glioblastoma multiforme
Metastatic kidney cancer
Intestinal bleeding
Heart failure
Opening of healed wounds
Used off label to slow the progression of neurovascular muscular degeneration, administration by intravitreal injection.
AlemtuzumabCause antibody-dependent cell-mediated toxicity.It binds to CD52 antigen and causes lysis of leukemic cells.Chronic B cell lymphocytic leukemia.Neutropenia
It is also used to treat multiple sclerosis relapse.
PembrolizumabBinds to PD-1 receptors and antagonizes its interaction with PD-L1 and PD-L2.Melanoma,Merkel cell carcinoma,Lung cancer,Classical Hodgkin lymphoma,Kidney cancer,B cell lymphoma,Liver cancer.Alopecia
Bradycardia or
It is often administered when metastases have occurred and other drugs are not responding.
NimotuzumabBinds to the extracellular domain of HER-2/neu receptors to cause their downregulation.
Antiangiogenic drug.
Breast cancer,Metastatic gastric or gastroesophageal junction adenocarcinoma.Congestive heart failureIt causes toxicity when combined with anthracyclines.
Murine monoclonal antibodies.
They have a suffix -omab, derived purely from murine source and can cause allergy in humans.
TositumomabLinked with radioactive iodine, target and destroy certain cells in the body.Relapsed non-Hodgkin’s lymphoma.ThrombocytopeniaAlso used in diagnosis and investigations.
Chimeric monoclonal antibodies.
They have a suffix -ximab, have variable regions from murine source and constant regions from a human source. They can also cause allergy in humans.
CetuximabInhibits epidermal growth factor receptor
on the surface of cancer cells.
Colorectal cancerInterstitial lung disease
Low blood pressure
Difficulty breathing
It may be combined with irinotecan or administered alone in patients who cannot tolerate irinotecan.
RituximabIts Fab fragments bind to the CD20 antigen on the B lymphocytes and its Fc domain causes complement and antibody-dependent, cell-mediated cytotoxicity of the B-cells.Post-transplant lymphoma
Chronic lymphocytic leukemia
Cardiac arrhythmias
It may also be used to treat multiple sclerosis and systemic lupus erythematosus, the autoimmune disorders.
IsatuximabInhibits the C38 ectoenzymes activity.
Antibody-dependent cell-mediated cytotoxicity.
Multiple myelomaAnemia
It is combined with pomalidomide and dexamethasone in multiple myeloma patients.
Human monoclonal antibodies.
Thay have suffix -umab and are purely derived from a human source.
CanakinumabBlocks proteins that cause inflammation and immune responseAuto-inflammatory syndromesDizziness
Urinary tract infections.
Also used to treat Sudden Juvenile Idiopathic Arthritis.
PanitumumabBinds to epidermal growth factor receptor (EGFR) and inhibit its activationMetastatic colorectal cancerArrhythmia, Difficulty breathingOnly RAS tumors.
IpilimumabBlocks the activity of cytotoxic T-lymphocyte antigen-4 (CTL4) and sustains T- cell response against tumor cells.Melanoma that cannot be cured by surgery
Colorectal cancer
It is combined with nivolumab to treat kidney cancer.
OfatumumabActivates the immune system and cause phagocytosis by targeting the CD20. Antibody-dependent, complement-dependent cytotoxicity.Chronic lymphocytic leukemiaTachycardia
It may be combined with chlorambucil.
It can cause reactivation of hepatitis B.

Other side effects occur as hypersensitivity reaction at first infusion, it could be managed with prophylactic glucocorticoids and/or antihistamines administration.

Anti-EGF-R antibodies may cause an acneiform rash that respond poorly to topical steroid creams.