Immune Checkpoint Inhibitors: The New Breakout Stars in Cancer Treatm | Page 2

Introduction
It only takes one hit to transform an indie film actor into a Hollywood superstar. But once they’re the Hollywood
darling starring in the latest big-budget blockbuster, it only takes one misstep to quickly fall out of favor with
the public.
Much the same can be said for some of what promised to be the big-budget blockbusters developed during the
early years of immuno-oncology therapeutics. A new therapeutic with promise that suddenly has reports of a new,
potentially detrimental side effect, or a less than stellar response in one trial, fades from the spotlight and remains
only a cult favorite. Immune checkpoint inhibitors are the most recent therapeutics to break out as big stars, and
there are a few of these drugs that are now first-line treatments, but not many.
How will these rises and falls ultimately affect the landscape of oncology therapy development? How are these
successes and failures shaping the future ….?

For more information about the history of immuno-oncology and the path
we have traveled to reach our current knowledge, watch our webcast titled
Avoiding Pitfalls and Encouraging Success with Immuno-Oncology.

Immune Checkpoints
The increasing focus on immuno-oncology is based on
the long history of clinical and preclinical observations
that suggest there is an immune response to cancer.
With normal function, immune checkpoints control
excessive immune activation and prevent autoimmunity,
protecting healthy tissues from damage during an
immune response to a pathogenic infection (Figure 1).
T cell activity is governed by ligand-receptor
interactions, balancing co-stimulatory and
inhibitory signals, or immune checkpoints.
Despite over a century of research, more reliable success
with immunotherapies for cancer has been achieved
only relatively recently. We have come to recognize that
tumors deploy programs to evade immune response
using the entire 3 x 109 human genome for this
process. The goal of immunotherapy therefore is to
re-establish the ability of the immune system to a)
recognize and b) reject malignant, transformed cells.
However, in many cancers, these immune checkpoints
also appear to be a means by which tumors evade the
immune system (Figure 2).
2

Figure 1. Basic illustration of immunologic synapses between T cells and
dendritic cells

The research area currently considered the most
promising is that of immune checkpoint inhibitors,
such as programmed death-1 (PD-1) and the PD-1
ligand (PD-L1).
Our immune system has the ability to recognize and
eliminate cancer cells but the tumors actively cripple
the immune system, creating a shield against their
elimination by the immune system. Abnormal
expression of PD-L1 can occur on malignant cells,
which inhibits the recognition of tumor antigens by