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 Dr. Arun Warrier,Senior Consultant, Medical Oncologist Astermedcity,Kochi Cancer develops when cells in our body develop the potential to grow
uninhibited. Ageing, changes in lifestyle, exposure to toxins all interact in a
complicated manner leading to this change.
Immune system of the body has an important role in preventing the cells from
gaining the ability to proliferate without control and invade other organs by
spreading through blood stream which are the hall marks of cancer. Because of
this reason, patients with disease like HIV which cause immunosuppression have a
higher number of cancers. This weakening of immune system in elderly persons
without any risk factors increases their risk of developing cancers.
Historically, Galen a renowned Greek physician, had documented the relation
between immune response and cancer. William Bradley Coley who is known today as
the Father of Immunotherapy described cancerous growths disappearing after skin
infections. Such spontaneous remissions are extremely rare, happening in 1 out
of 60,000- 100,000 cases. Over the last 100 years, contributions from scientists
all over the world were instrumental to understand the fascinating interplay
between immune regulation and cancer. In 2018, Nobel Prize was awarded to James
Allison and Tasuku Honjo for their meticulous work on checkpoint molecules as
potential therapeutic targets.
Antibody based therapies were the initial ones to be used in for treatment of
cancer. Antibodies are made by the body to mark out cancer cells. In 1997,
Rituximab, which targets the CD 20 antibody on lymphoma cells, became the first
monoclonal antibody to be approved.
In the last 25 years, lakhs of patients across the world were saved using
Rituximab either alone or in combination with chemotherapy in various types of
lymphomas. Trastuzumab, another monoclonal antibody against Her 2-receptor
expressed in 25 % of breast cancers has also improved cancer outcomes for a
significant number of patients.
Cancer cells can protect themselves from immune system by stimulating
checkpoints. This helps them to hide from the protective cells of the body.
Checkpoint inhibitors block these points, thus restoring the capacity of body to
fight against cancer.
In 2011, Ipilimumab was the first such drug to be approved for treatment of
Melanoma. In a short span of time, several other inhibitors of the PD-1 receptor
or its ligands, PD-L1 and PD-L2, were approved worldwide. Nivolumab,
pembrolizumab, atezolizumab, durvalumab, and avelumab all showed significant
improvement in outcomes of several cancers. Elegant clinical trials were
designed to monitor the efficacy in multiple cancers and based on them, they are
approved for use in specific cancers. Notable among them are lung cancer,
melanoma, bladder cancer and colon cancer.
There is a scientific rationale for use of these drugs and they cannot be given
for all cancers. In lung cancer, we can measure the PDL1 receptor expression on
the lung cancer specimen after doing a biopsy. If the level of expression is
more than 50 %, Pembrolizumab as a single drug is more effective than even
chemotherapy. Meanwhile for lung cancers which lose response to chemotherapy,
these drugs can be used irrespective of PD L1 expression. Better understanding
of such predictive markers are needed to ensure that those who respond the best
are offered immunotherapy as these drugs are expensive. A proportion of patients
on these drugs can also develop side effects, so close medical monitoring is
needed.
Review of patient records have shown that almost 20- 30 % of advanced cancer
patients who were treated with these drugs survived, compared to less than 5 %
of historical controls.
Immunosuppressive agents, Cytokines, Oncolytic viruses, Cancer Vaccines are all
being developed to engineer the immune system to fight against cancer.
CAR T cell therapy seems to be the one which maybe used more frequently
in near future. CAR T cell therapy involves the isolation of patient's T cells
which are tumor-specific, modification and multiplication of those cells in the
laboratory and then re-injection back to the patient circulation.
Dramatic responses in chemotherapy failed patients have resulted in the approval
of CAR T cell therapy in relapsed leukemias and lymphomas. In the future,
immunotherapy drugs may be used more frequently in adjuvant settings to prevent
relapse of the disease after a curative treatment. Identifying the subset of
patients who would benefit the most based on biomarker testing would be the most
challenging aspect. Rather than replacing Chemotherapy, they will have a role
along with chemo and other targeted agents in the continuum of care for cancer
patients.
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