The Week India - July 29, 2018

COVER STORY

22 THE WEEK · JULY 29, 2018

HEALTH

Immunotherapy

Scientists have been trying to harness our im-

mune system to attack cancer cells since the

1940s. Over the past fi ve to ten years, immuno-

therapy has emerged as the major cancer treat-

ment approach. It has revolutionised treatments

of some of the refractory cancers such as mela-

noma, lymphoma, lung cancers and bladder

cancer.

There are four different types of immunother-

apy approaches: monoclonal antibodies, CAR

T-cell therapies, immune checkpoint inhibitors

and cancer vaccines.

Monoclonal antibodies: The immune system

can make a large number of antibodies to attack

foreign substances, such as cancer. An antibody

is a protein that attaches to a specifi c protein

called an antigen. Scientists have designed many

antibodies that specifi cally target a certain anti-

gen, such as one found on cancer cells. They can

then make many copies of that antibody in the

lab. These are known as monoclonal antibodies

(mAbs). Monoclonal antibodies such as trastu-

zumab (for Her-2 positive breast cancer), and

rituximab (CD20 lymphoma) have completely

changed the treatment of this diagnosis. There

are antibody drug conjugates, which are one of

the highly targeted drugs, combined with mono-

clonal antibodies.

CAR T-cell therapy: Our immune system keeps

track of all the substances in our body. If the

immune system doesn’t recognise any new sub-

stances, it will raise an alarm and attack them.

CAR T-cell (Chimeric Antigen Receptor T-cell)

therapy is a promising new way to get immune

cells called T-cells to fi ght cancer by changing

them in the lab so they can fi nd and destroy

cancer cells. CAR T-cell therapies are otherwise

categorised as a type of gene or cell therapy, or

an adoptive cell transfer therapy. There are two

CAR T-cell therapies approved—for recurrent

acute lymphoblastic leukemia and refractory

non Hodgkin’s lymphoma.

Immune checkpoint inhibitors (PD-1 and PDL-

1 inhibitors): It is important for our immune

system to recognise what is normal and what is

foreign. By doing this the immune system can at-

tack the foreign or cancer cells and leave the nor-

mal cells alone. But immune cells have breaks

or checkpoints to control when an immune cell

will or will not attack or mount an immune re-

sponse. Cancer cells effectively use these check-

points to avoid being attacked by the immune

system. But drugs that target these checkpoints

such as PD-1 and PDL-1 blockers hold a lot of

promise as cancer treatments.

Vaccines to help treat cancer: Cancer vaccines

help the immune system to attack cancer cells

in the body. Cancer vaccines may be made up

of cancer cells, parts of cells or pure antigens.

Sometimes a patient’s own immune cells are

removed and exposed to these substances in

the lab to create the vaccine. Once the vaccine

is ready, it is injected into the body to increase

the immune response against cancer cells. One

of my colleagues at Cleveland Clinic, Dr Vince

Tuohy, has developed a vaccine to prevent cer-

tain types of breast cancer in preclinical mod-

els. Now we are planning to take that preclini-

cal concept to see if it can work in patients.

Gene editing

Gene editing is a technology that gives scien-

tists the ability to change an organism's DNA.

This will allow scientists to add, delete or

modify genetic material. Several approaches to

genome editing are used. One of the most com-

monly used ones is CRISPR-Cas9 (clustered

regularly interspaced short palindromic re-

peats) and CRISPR-associated protein 9. This

is an exciting technology—it is faster, cheaper,

more accurate, and more effi cient than other

existing genome editing methods.

If the ongoing research continues to show the

same promise, it can potentially prevent and

treat many illnesses, including blood disorders

such as sickle cell disease, hemophilia and can-

cer.

Cancer treatment has changed dramatically

in the past 16 years I have been doing cancer

treatment and clinical research. It is amazing

that some of the most non-curable cancers

have transformed into chronic disease or cur-

able disease. But we have a long way to go.

Countries like India have to create a safe and

ethical environment for clinical trials. Other-

wise, our patients will not be able to access

novel therapies in a timely manner.

Abraham is director of breast oncology program and

professor of medicine, Cleveland Clinic, Cleveland, US.