Home' Australasian BioTechnology : Vol 26 No 2 Contents Australasian BioTechnology | Volume 26 | Number 2
One way that is being actively explored to increase response
rates is for immunotherapies to be used in combination with
themselves, or with other therapies. Again in melanoma,
the combination of Opdivo® with YERVOY® has pushed
response rates into the 50 per cent and above range;
however, the extra activity comes at a cost---both financially
and clinically. High-priced therapies (often at a cost of
more than $100,000 per patient per annum per drug) create
challenges for the healthcare system. For the individual,
doubly activating the immune system increases the
incidence and severity of side effects: particularly debilitating
inflammatory conditions, such as inflammatory bowel disease.
The immune system is a powerful beast, and there are good
reasons why it is subject to natural control mechanisms such
On the treatment horizon is a range of cellular therapies,
which represent another dimension of the immuno-oncology
arsenal. It is now possible to engineer and expand T cells
targeting specific TAAs by transfecting the cells with chimeric
antigen receptors (CARs) to create CAR-T cells. These cells do
not need to be activated through the normal T cell activation
pathways; they are ready to seek out and destroy tumour
cells expressing the cognate TAA. In clinical trials in patients
with rare leukaemias, such as acute lymphoblastic leukaemia
(ALL), response rates of 95 per cent have been achieved
using CD19-targeted CAR-T cells in patients who have failed
all existing therapies. To describe this as unprecedented is a
gross understatement! However, despite such extraordinary
results (and the associated optimism and hype), the CAR-T
approach is yet to prove itself in other tumour types,
particularly solid tumours.
Finally, another form of cellular immunotherapy that is
beginning to gain momentum is to leverage the innate immune
system, particularly through the activity of natural killer (NK)
cells. Mechanisms for the activation of endogenous NK cells
are being explored, as is the infusion of exogenous NK cells. In
some ways, this brings the field of immuno-oncology full circle.
It is now known that bacterial cell components are natural
activators of the immune system (through, for example, binding
of bacterial DNA to toll-like receptors on immune cells), and
it is quite likely that the occasional beneficial effects obtained
with 'Coley's toxins' were due, at least in part, to non-specific
stimulation of innate immunity.
So, where to from here? It is reasonable to argue that we are
still in the early stages of the immuno-oncology revolution. It is
also reasonable to argue that prior oncology drug development
efforts (whether successful or not) needs to be reconsidered
in light of treatments such as checkpoint inhibitors. It is likely
that treatments like cancer vaccines, and even chemotherapy,
may be much more effective in the context of an immune
system 'with the handbrake released'. Similarly, other emerging
approaches, such as oncolytic viruses, need to be assessed in
combination with checkpoint inhibitors. There is a huge amount
of work to be done, both pre-clinically and clinically.
One thing seems certain: after a gestation period of more than
a century, manipulating and using the immune system to treat
existing disease, as well as to prevent disease recurrence, will
finally be entrenched as a central feature of cancer therapy.
Dr Ian Nisbet is a partner in the biotechnology consulting
company Afandin Pty Ltd. He is actively involved in cancer
drug development, with multiple companies; he is the part-
time CEO of Cancure Pty Ltd, which is developing a portfolio
of cancer drugs that includes both immunotherapies and
targeted therapies; he is a co-founder and executive director
of Senz Oncology Pty Ltd, which is developing a small-molecule
treatment for acute myeloid leukaemia (AML); he is a co-founder
and corporate adviser to Cartherics Pty Ltd, which is developing
a next-generation CAR-T platform; and he is chairman of
vivoPharm Pty Ltd, a preclinical contract research organisation
that specialises in cancer pharmacology. He is also an Industrial
Fellow at the Australian Institute for Bioengineering and
Nanotechnology (AIBN) at the University of Queensland.
ERBITUX® IS A REGISTERED TRADEMARK OF ELI LILLY AND COMPANY.
HERCEPTIN® IS A REGISTERED TRADEMARK OF GENENTECH USA, INC.
KEYTRUDA® IS A REGISTERED TRADEMARK OF MERCK AND CO.
OPDIVO® AND YERVOY® ARE REGISTERED TRADEMARKS OF BRISTOL-MYERS SQUIBB
PROVENGE® IS A REGISTERED TRADEMARK OF DENDREON CORP.
RITUXAN® IS A REGISTERED TRADEMARK OF BIOGEN, INC.
So, where to from here? It is
reasonable to argue that we are still in
the early stages of the
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