OUTLOOK CANCER IMMUNOTHERAPY

CALLING CELLS TO ARMS

Increased understanding of immune- and tumour-cell biology has led to an
explosion of research into potential ways to harness the immune system to kill cancer.
By Emily Elert.

NATURAL IMMUNE RESPONSE

The body’s specific immune response begins when specialized immune cells present pieces Effector T cell
of foreign matter, called antigens, to immature immune cells in the lymph nodes. Stimulates proliferation of B cells,
which produce antibodies.

Immature T cell Memory T cell

Retains memory of antigen
and responds rapidly to
Proliferation
future encounters.
Maturation

Regulatory T cell
Produces cytokines that keep
immune response in check.

1 Roaming dendritic 2 DC presents 3 Activated T cell releases

cell (DC) captures foreign antigen to cytokines to stimulate
Killer T cell
and processes immature T cell. immune response, including
foreign material. T cell proliferation and maturation. Targets and kills foreign cells.

THERAPEUTIC APPROACHES
Current cancer immunotherapies can be broken down into three major types: non-specific therapies, monoclonal antibodies and vaccines.

NON-SPECIFIC IMMUNOTHERAPIES MONOCLONAL ANTIBODIES VACCINES

These drugs include cytokines and other These proteins stick to specific antigens, either Vaccines are made from cancer cells, parts of cells
chemicals that stimulate a general immune directly affecting cells or tagging them for or antigens designed to stimulate the immune
response. Most likely to be used as adjuvants to destruction. Uses include: system to attack a tumour. Multiple approaches are
other therapies, such as vaccines. being tested, including DC vaccines.

Carrying drugs or toxins to target cells. Antigen

1 A patient's DCs are removed,
stimulated and re-infused
Synthetic cytokines with a cancer-specific
1 Drug
drive growth and antigen.
proliferation of
immune cells.
Cancer cell

Dendritic
OR cell
Tagging cell for destruction by immune cells.

Killer immune cell Treated DCs present

2
the antigen to other
immune cells.

Immune cell
Immature T cell

OR
2 Abundant immune 3 Activated immune cells,
cells target and kill Blocking signalling pathway to halt growth primed to recognize the
cancer cells. or proliferation. cancer, mature and
proliferate.

Helper
Cancer
Cancer cell T cell
cell

Killer T cell

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 CANCER IMMUNTHERAPY OUTLOOK

SEARCHING FOR SYNERGY A DURABLE CONCEPT

Single immunotherapies have been only modestly effective, so researchers are searching for

WELLCOME LIBRARY
synergistic combinations of drugs. The ideal attack below includes existing therapies, drugs in After reading that a
clinical trials and theoretical compounds. patient’s tumour disappeared
after a bacterial infection,
1 Tumour microenvironment 2 Vaccine surgeon William Coley begins
injecting cancer patients with
Initial therapy increases vulnerability of Cancer-specific antigens,
bacteria (now known to be
cancer cells to immune attack. non-specific adjuvants, and
Streptococcus pyogenes).
molecules to increase
immune activity.

DR MARK J. WINTER/
SCIENCE PHOTO LIBRARY
Drugs block Biologist
Modified virus invades
anti-apoptosis Cytokines Paul Ehrlich
cancer cells and causes
pathways in tumour activate T cells suggests that
cell lysis, eliciting innate
cells and inhibit Antibodies immune cells
immune response.
regulatory T cells. promote actively patrol the
Antigen- activation and body to suppress
presenting block inhibition the growth of
cells (APCs) of T cells cancerous cells.
process and
display tumour
antigens. APC Tumour- Mice show immunity to tumour cells
mobilizers specific after cancer is allowed to grow and then
activate APCs antigens surgically removed, suggesting the existence
of tumour-specific antigens.

DAVID SCHARF/SCIENCE PHOTO LIBRARY

Discovery of interferon, an immune-
3 Lymph nodes stimulating cytokine that will eventually be
Killer T cells
APCs present vaccine used as a non-specific cancer immunotherapy.
release toxins to
antigens to immature
destroy
T cells, which mature
tumour cells.
and proliferate. Bacillus
Calmette-Guérin (BCG),
4 Blood stream Helper T cell a tuberculosis vaccine,
Activated T cells is shown to inhibit
migrate to site Killer T cell tumour growth in mice.
of tumour.

NIBSC/SCIENCE PHOTO LIBRARY

Dendritic
cells described by
Ralph Steinman
and Zanvil A. Cohn.
Steinman won the
Nobel prize for this
discovery.

IMMUNOTHERAPIES ON TRIAL
Discovery of T-cell antigen receptors,
The number of cancer immunotherapies in phase III clinical trials has risen sharply since the early 1990s,
which detect antigens presented by other
reflecting renewed interest in immune-based cancer treatments among researchers and drug-makers.
immune cells and ramp up the immune
response.
Monoclonal antibodies (157 trials) Ipilimumab, a CTLA-4 Combination treatment
specific monoclonal with ipilimumab and
Non-specific immunotherapies (269 trials)
antibody, increases nivolumab, a PD-1
Vaccines (113 trials) First humanized antibodies approved
survival in advanced blocker, reduces tumour
by the US Food and Drug Administration (FDA).
melanoma. size in melanoma.

40
This still-active trial looks Sipuleucel-T (the only The first
DR MARK J. WINTER/

at whether the bacterium cancer vaccine on the SCIENCE PHOTO LIBRARY

35 monoclonal
Corynebacterium market) starts trials antibody for
granulosum can prevent in patients with prostate
Number of trials starting (cumulative)

cancer, Rituximab,
30 cancer recurrence. cancer. approved by the
FDA for treating
25 non-Hodgkin’s
Monoclonal antibodies enter
phase III trials to detect and lymphoma.
20 treat lymphoma.

15
Phase III trial tests
10 interferon in combination
with chemotherapy for First therapeutic cancer vaccine,
colon cancer. Oncophage, wins approval in Russia for
5 treating kidney cancer.

0
1971 1974 1977 1989 1992 1995 1998 2001 2004 2007 2010 2013 FDA approves Dendreon’s cancer
vaccine, Provenge (sipuleucil-T), for the
Year trial began treatment of prostate cancer.

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