A monoclonal antibody is an antibody produced by cloning a particular white

blood cell. It is derived from a one cell clone (a single B cell clone). All
subsequent derived antibodies are traced back to a distinctive parent cell in
this way. Therefore, a single, pure form of antibody is a monoclonal antibody.
Monoclonal antibodies are concentrated forms of specific antibodies that
function against coronavirus.

Monoclonal Antibodies
- Monoclonal antibodies are laboratory produced antibodies designed to recognize and
bind to specific receptors found on the surface of cells. They are derived from natural
antibodies; complex proteins derived from a single B cell made by the body's
immunological defense system to recognize and fight foreign invaders such as bacteria
and viruses.

- The blue and green Y-shaped forms in this picture represent monoclonal antibodies in the
process of binding to receptors found on the surface of cells. Credit: Anna Tanczos,
Wellcome Images.
DISCOVERY
In the 1890s Emil von Behring and Kitasato Shibasaburo observed that blood taken from
animals infected with diphtheria or tetanus could give immunity to other animals not previously
exposed to such diseases. Following this Paul Ehrlich identified that the source of protection in
blood came from antibodies and hypothesized that antibodies could be used one day as magic
bullets for medicine.

Thereafter, scientists began hunting for a means to isolate and purify individual antibodies from
the billions produced by the body's defense system. This was finally achieved in 1975 by
Georges Kohler and Cesar Milstein, based at the Laboratory of Molecular Biology in Cambridge,
UK, with their development of a technique to produce monoclonal antibodies.

HOW DO THEY WORK?

Antibodies are proteins produced by our immune system and are one of the
main ways the body defends itself against diseases.

Monoclonal antibodies work in the same way too.

They bind to their specific target, without harming anything else in their way.
This target is not always a ‘foreign intruder’, like a virus. Antibodies can be
designed to attach to different molecules in the body, for example, to turn
down the immune response when it overreacts; this phenomenon, which also
happens with some Covid-19 patients, is called a ‘cytokine storm’.

HOW THEY ARE MADE?

Making monoclonal antibodies is complex and expensive.

First, scientists extract the relevant antibodies from human blood. Then they
replicate and manufacture them in large quantities. 

Most monoclonal antibodies are produced in Chinese hamster ovary cells

which are typically grown in large bioreactors for around 10 to 15 days. The
resulting antibodies are then purified and packaged so they can be easily
administered.

This whole process takes a long time and uses costly materials.

WHAT DISEASES ARE THEY USED FOR?

The majority of the monoclonal antibodies on the market are for

noncommunicable diseases, such as autoimmune diseases, like rheumatoid
arthritis and cancer.

In the past few decades, cancer immunotherapies have saved the lives of
millions of people around the world. Monoclonal antibodies have transformed
the way we treat multiple cancers, including breast cancer, for which the drug
Herceptin has been a game changer.
Out of more than 100 licensed monoclonal antibodies, only seven are for
treating and preventing infectious diseases – though many more are in
development, including candidates for SARS-CoV-2, the virus that causes
Covid-19.

Importance
It is difficult to overstate the extent to which monoclonal antibodies have
transformed healthcare since their introduction in 1975. One of their key
advantages is that they are very precise in their target and have a very
high degree of sensitivity. This has makes them highly versatile tools for
basic research, diagnostics and therapeutics. In 2010 the combined
global monoclonal antibody diagnostics and therapeutics market was
valued at US$55 billion. In 2012 there were more than 30 monoclonal
antibody drugs on the worldwide market. Of these ten were blockbuster
drugs, each of them generating more than US$1 billion per year. Today
monoclonal antibody drugs account for a third of all new treatments
introduced.

Application
The production of monoclonal antibodies involves several steps. In the
first instance a laboratory animal is injected with a desired target to
stimulate their immune system. Following this, antibody producing cells,
B lymphocytes, are harvested from the animal's spleen and fused with
an immortal myeloma cell line to create hybrid cells, or hybridomas. The
hybrid cells are then screened to find those that secrete antibodies with
the desired specificity for a particular target. Once identified the hybrid
cell is cloned to establish a hybridoma colony. This colony is then
maintained in a culture medium to provide a continual supply of
monoclonal antibodies. Each of the antibodies secreted by the hybrid
cell is identical (monoclonal) and has the capacity to bind to a specific
receptor found on the surface of a cell.

Advantages:

 Can produce large quantities of identical antibody. Batch to batch

homogeneity.

 High specificity to a single epitope. Reduced probability of cross

reactivity.

 Can provide better results in assays requiring quantification of the

protein levels.

Disadvantages:

 Significantly more expensive to produce.

 Requires significantly more time to produce and develop the hybridized

clone.

 Small changes in the epitope's structure often render the monoclonal

antibody unable to detect the target protein.

 Less ideal for application requiring quick capture of the target protein.

 More sensitive to pH and buffer conditions.

What are the side effects of monoclonal antibodies?

Monoclonal antibodies can cause side effects, which can differ from person to person. The ones
you may have and how they make you feel will depend on many factors, such as how healthy
you are before treatment, your type of cancer, how advanced it is, the type of monoclonal
antibody you are receiving, and the dose.

Doctors and nurses cannot know for sure when or if side effects will occur or how serious they
will be. So, it is important to know which signs to look for and what to do if you start to have
problems.

Like most types of immunotherapy, monoclonal antibodies can cause skin reactions at the needle
site and flu-like symptoms.

Possible side effects of monoclonal

antibodies
Monoclonal antibodies are given intravenously (injected into a vein). The antibodies
themselves are proteins, so giving them can sometimes cause something like an
allergic reaction. This is more common while the drug is first being given.
Possible side effects can include:

 Fever
 Chills
 Weakness
 Headache
 Nausea
 Vomiting
 Diarrhea
 Low blood pressure
 Rashes
Compared with chemotherapy drugs, naked mAbs tend to have fewer serious side
effects. But they can still cause problems in some people. Some mAbs can have side
effects that are related to the antigens they target. For example:
  Bevacizumab (Avastin) is an mAb that targets a protein called VEGF that
affects tumor blood vessel growth. It can cause side effects such as high blood
pressure, bleeding, poor wound healing, blood clots, and kidney damage.
 Cetuximab (Erbitux) is an antibody that targets a cell protein called EGFR,
which is found on normal skin cells (as well as some types of cancer cells).
This drug can cause serious rashes in some people.

The chance of side effects depends on the dose, type of steroid and length of
treatment. Some side effects are more serious than others. Common side
effects of systemic steroids include:
 1. Crushing Syndrome
Cushing syndrome is caused by prolonged exposure to high circulating levels of cortisol
Cushing syndrome can develop from taking oral corticosteroid medications, such
as prednisone, in high doses over time. Oral corticosteroids may be necessary to treat
inflammatory diseases, such as rheumatoid arthritis, lupus and asthma. They may also
be used to prevent your body from rejecting a transplanted organ.

2. Osteoporosis
Corticosteroids tend to both reduce the body's ability to absorb calcium and
increase how fast bone is broken down. The more of these drugs you take and the
longer you take them, the greater your risk of developing osteoporosis.

3. Retardation of Growth
Blunting of pulsatile growth hormone release, inhibition of insulin-like growth factor-
1 bioactivity, osteoblast activity and suppression of collagen synthesis and adrenal
androgen production are all known mechanisms by which corticosteroids can inhibit
growth. (by causing bones to mature too fast and stop growing at an early age)

4. Thinning of Skin
A number of studies2,3 confirm that inhaled corticosteroids, even at low doses, 4 can
cause skin atrophy (i.e. paper-thin skin5) and purpura. The mechanism appears to
involve a reduction in collagen synthesis.

5. Immunosuppression
Corticosteroids cause immunosuppression mainly by sequestration of CD4+ T-
lymphocytes in the reticuloendothelial system and by inhibiting the transcription of
cytokines. Corticosteroids can raise your risk of infections because they have a wide
range of effects on the immune system. The medication dosage has a big impact on
the risk of infection.

6. Cataracts + Glaucoma

The specific types of cataracts known to be promoted by steroids are called

subcapsular cataracts. These cataracts develop near the back of the eye lens, forming
opaque patches that inhibit the passage of light to the retina. Subcapsular cataracts
often produce glare or halos at night, interfere with reading and limit vision in bright
conditions. Patients taking corticosteroids should schedule regular screenings with their
eye doctor to diagnose any cataract development. If diagnosed early, your eye
physician can make recommendations to help slow cataract development.

7. Oedema
Because these steroids specifically for example (cortisone) is involved in regulating the
body's balance of water, sodium, and other electrolytes, using these drugs can promote
fluid retention and sometimes cause or worsen high blood pressure. Corticosteroids
can cause sodium retention through a direct action on the kidney. This can result in fluid
retention and hypertension.

8. Suppression of Hypothalamic Pituitary Axis

Chronic use of corticosteroids inhibits the function of the hypothalamic-pituitary-
adrenal axis by negative feedback, which may cause adrenal insufficiency also after
the cessation of corticosteroid treatment (4, 6). Adrenal insufficiency is a serious,
potentially life-threatening side effect of corticosteroid use. Adrenal suppression, (AS)
Cortisol production by the adrenal glands is suppressed by exposure to additional
steroids used to treat illness. The pituitary and hypothalamus stop signaling the
adrenals to produce cortisol as a result of therapeutic steroids in the body. Over time,
the adrenals can atrophy.

9. Teratogenic
They are considered relatively safe in pregnancy when used in low doses and are
designated as category B medications. Nonetheless, corticosteroids may increase the
maternal risk of hypertension, edema, gestational diabetes, osteoporosis, premature
rupture of membranes, and small-for-gestational-age babies.
 10. Emotional Disturbances
The most commonly reported corticosteroid-induced psychiatric disturbances
are affective, including mania, depression, or mixed states. Most often, patients
receiving short-term corticosteroid therapy present with euphoria or hypomania,
whereas long-term therapy tends to engender depressive symptoms.

11. Raises Blood Pressure/Hypertension

The principal mechanism of corticosteroid- induced hypertension is the
overstimulation of the mineralocorticoid receptor, resulting in sodium retention in
the kidney. This results in volume expansion and a subsequent increase in blood
pressure. Corticosteroid-induced hypertension may respond to diuretic therapy.
Prednisone raises blood pressure in many people who take it. One reason is that
prednisone and other corticosteroids cause the body to retain fluid. Extra fluid in the
circulation can cause an increase in blood pressure.

12. Obesity
Steroids cause weight gain by altering the body's electrolyte and water balances,
as well as its metabolism — the way it uses and stores lipids, amino acids, protein,
carbohydrates, and glucose, among other things. These factors contribute to weight
gain by causing: increased appetite. fluid retention. Steroids affect your
metabolism and how your body deposits fat. This can increase your appetite, leading
to weight gain, and in particular lead to extra deposits of fat in your abdomen.

13. Increase Body Hair Growth

One of the numerous potential side–effects of prednisone and other forms of
corticosteroid treatment is hirsutism — excessive growth of body hair. Patients vary
in the degree to which this side–effect of steroids occurs. This occurs when your body
is exposed to high levels of the hormone cortisol. It can develop from your adrenal
glands making too much cortisol or from taking medications such as prednisone over a
long period.

14. Diabetes Mellitus

Prednisone and other steroids can cause a spike in blood sugar levels by making
the liver resistant to insulin. The pancreas produces insulin to control blood sugar
levels. Diabetes can result from a fault in the way that the body reacts to insulin or a
problem with the production of insulin in the pancreas. Corticosteroids increase insulin
resistance thus allowing blood glucose levels to rise and remain higher.

15. Striae
Corticosteroid creams, lotions, and pills can cause stretch marks by decreasing the
skin's ability to stretch. Cushing's syndrome, Marfan's syndrome, Ehlers-Danlos
syndrome, and other adrenal gland disorders can cause stretch marks by increasing the
amount of cortisone in your body. Although early skin thinning can disappear if the
topical corticosteroid is discontinued, prolonged use can cause permanent stretch
marks (striae). Stretch marks usually occur on the upper inner thighs, under the arms,
and in the elbow and knee creases.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1927922/#:~:text=Pre
%2Dexisting%20striae%20have%20been,rather%20than%20to
%20mechanical%20tension.

Warnings and Precautions/Interactions

Taking a few precautions before, during and after you use corticosteroids that
can help prevent some serious problems.

If you've been taking glucocorticoids for two weeks or more, don't stop taking the drug
suddenly unless your doctor tells you otherwise.

Stopping the drug "cold turkey" could send your body into crisis mode.

Certain medical conditions may affect the use of this medication. Tell your doctor if
you have any health conditions.

Ask your doctor about glucocorticoids if you:

 Have a weakened immune system or are at increased risk of an infection (like

HIV/AIDS, herpes simplex infection of the eye, tuberculosis, fungal infection,

 stomach or intestinal problems

 have had a recent surgery or serious injury
 Have an active infection, including measles or chicken pox
 Have high blood pressure, congestive heart failure, or diabetes
 Recently had a heart attack
 Have a disorder affecting your digestive tract, like inflammatory bowel
disease, peptic ulcer disease, or holes in your intestines
  Have seizures
 Have a mood disorder
 Have a condition involving hormone balance, like a thyroid
disorder or osteoporosis

• Steroids increase your risk of infection so you might want to consider a flu shot
before you start the medication. Avoid all immunizations while on steroids unless
your doctor recommends otherwise. You also need to stay away from anyone
who has had a live virus vaccine, like measles, mumps, rubella or polio; you
could catch the virus from them. 
•  In the past, steroids were linked to birth defects, low birth weight and
premature delivery. Later studies haven’t found increased risks in pregnant
women. To be safe, you may still want to use an effective birth control method.
•  Insomnia is a common side effect of corticosteroids, so you may want to talk to
your doctor about taking the whole dose in the morning.
•  Steroids can interact with hundreds of medications. Be sure to tell your doctor
all the prescription and over-the-counter drugs you take. You may need to stop
some of them or find another type of anti-inflammatory.
•  Side effects of corticosteroids can persist long after you stop taking them so
continue seeing your doctor regularly.
 Corticosteroids can also alter the effects of other medications. However, the
likelihood of interactions happening with steroid sprays or injections is low.

Be careful what you eat when taking this medication, too. Certain steroids shouldn’t
be taken with food, as interactions may occur. Avoid taking this drug with grapefruit
juice.

Tobacco and alcohol can also cause interactions with certain medications. Make sure
to talk to your doctor about the effect these may have on corticosteroids.

Yt link: https://www.youtube.com/watch?v=tvivILLAWRI
https://www.medscape.com/viewarticle/582385_4#:~:text=The%20principal%20mechanism
%20of%20corticosteroid,may%20respond%20to%20diuretic%20therapy.

https://aiunited.org/wp-content/uploads/STEROIDS-ASTHMA.pdf
https://www.hss.edu/conditions_steroid-side-effects-how-to-reduce-corticosteroid-side-
effects.asp

https://pubmed.ncbi.nlm.nih.gov/17900234/#:~:text=Although%20the%20mechanism%20of
%20steroid,interact%20to%20generate%20steroid%20cataracts.

https://pubmed.ncbi.nlm.nih.gov/14766378/#:~:text=Corticosteroids%20cause
%20immunosuppression%20mainly%20by,inhibiting%20the%20transcription%20of
%20cytokines.

https://www.medsafe.govt.nz/profs/puarticles/atrophy.htm#:~:text=A%20number%20of
%20studies2,a%20reduction%20in%20collagen%20synthesis.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4319193/#:~:text=Blunting%20of%20pulsatile
%20growth%20hormone,which%20corticosteroids%20can%20inhibit%20growth.

https://www.cedars-sinai.org/health-library/diseases-and-conditions/c/corticosteroid-induced-
osteoporosis.html#:~:text=Causes%20and%20Risk%20Factors&text=Corticosteroids%20tend
%20to%20both%20reduce,your%20risk%20of%20developing%20osteoporosis.

https://www.mayoclinic.org/diseases-conditions/cushing-syndrome/symptoms-causes/syc-
20351310#:~:text=Cushing%20syndrome%20can%20develop%20from,from%20rejecting%20a
%20transplanted%20organ.

https://www.medscape.com/answers/335186-187623/are-corticosteroids-safe-for-pregnant-
women-with-rheumatoid-arthritis-ra

https://www.mayoclinicproceedings.org/article/S0025-6196(11)61160-9/fulltext