First patient trials of DNA vaccine for leukaemia
16 Feb 2011
A new DNA vaccine to treat leukaemia that has been developed
by scientists from the University of Southampton is being trialled on
patients for the first time in the UK.
In the trial the vaccine will be used on a selected group of
volunteers who have either chronic or acute myeloid leukaemia — two
forms of bone marrow and blood cancer.
Scientists believe they can control the disease by vaccinating
patients against a cancer-associated gene (Wilm's Tumour gene 1),
found ‘expressed’ in almost all chronic and acute leukaemias.
Leukaemia, which accounts for 220,000 deaths worldwide each year,
is a malignant disease of the bone marrow and blood characterised by
the uncontrolled accumulation of blood cells.
Acute myeloid leukaemia (AML) is a cancer of the myeloid line in
blood cells and is characterised by rapid growth of abnormal white
blood cells that accumulate in the bone marrow and interfere with
the production of normal blood cells. Chronic myeloid leukaemia
(CML) is a type of cancer that causes the body to produce large
numbers of immature and mature white blood cells.
A team of researchers and health practitioners, led by Professor
Christian Ottensmeier of the University of Southampton Experimental
Cancer Medicine Centre and Dr Katy Rezvani of Imperial College
London and Imperial College Healthcare NHS Trust, hope to recruit up
to 180 patients to the trial which will take place at hospitals in
Southampton, London and Exeter over the next two years.
"In chronic myeloid leukaemia, current treatment can reduce the
cancer but the drug needs to be taken indefinitely and has
unpleasant side effects. Prognosis of acute myeloid leukaemia is
currently poor and better treatments are urgently needed," said
Christian Ottensmeier, professor of experimental cancer medicine at
the University of Southampton and consultant oncologist at
Southampton University Hospitals NHS Trust.
"We have already demonstrated that this new type of DNA vaccine
is safe and can successfully activate the immune systems in patients
with cancer of the prostate, bowel and lung. We believe it will
prove to be beneficial to patients with acute and chronic myeloid
Dr Katy Rezvani, clinical senior lecturer at Imperial College
London and consultant haematologist at Imperial College Healthcare,
says: “At Hammersmith Hospital we have been using targeted leukaemia
drug therapies, like tyrosine kinase inhibitors, for over 10 years.
While these drugs are the first line therapy for chronic myeloid
leukaemia patients, they can rarely ‘cure’ the condition. This new
vaccine has the potential to improve the outcome of leukaemia
treatments and could serve as a method of managing solid tumours.”
Professor Freda Stevenson, an immunologist at the University of
Southampton who is also working on the study, adds: “I’m very
pleased with the results from the laboratory research, and am
optimistic the vaccine will be successful in making a real
difference to patients with myeloid leukaemia.”
In the study, each participant will receive six doses of DNA
vaccine over a six-month period, with further booster vaccinations
if successful. The vaccine will be administered in a groundbreaking
new way, using electroporation, in which controlled, rapid
electrical pulses create permeability in cell membranes and enable
increased uptake of biological material after its injection into
muscle or skin tissue. The electroporation system was developed by
the US pharmaceutical company Inovio.
The DNA vaccine was developed at the University with funding from
Leukaemia & Lymphoma Research and Cancer Research UK.
Grant, Scientific Director of Leukaemia & Lymphoma Research, adds:
"We are delighted to see this trial in leukaemia go ahead. It is an
important step for us to see the laboratory work on DNA vaccines
that the charity has supported take the next logical step into
clinical testing. The trial has undergone extensive international
peer review and we are very excited to see the first patients being
treated. We believe that this vaccine has real promise to improve
outcomes in patients with leukaemia."
The success of the vaccines will be measured over a two-year
survival period for acute myeloid leukaemia and by assessing the
immune system's response to the drug using a disease marker
(BCR-ABL) for chronic myeloid leukaemia.
The research is funded by the charity Leukaemia & Lymphoma
Research and the Efficacy and Mechanism Evaluation (EME) programme,
which is financed by the Medical Research Council (MRC) and managed
by the National Institute for Health Research (NIHR).
Inovio's CEO Dr J Joseph Kim, said: "This study expands Inovio's
long-standing relationship with the University of Southampton into
an important disease area. We are proud that Inovio will make a
significant contribution to this Phase II trial for these cancers
with clear unmet medical needs."
Inovio is developing a new generation of vaccines, called DNA
vaccines, to treat and prevent cancers and infectious diseases. Its
SynCon vaccines are designed to provide broad cross-strain
protection against known as well as newly emergent strains of
pathogens. These vaccines, in combination with Inovio’s proprietary
electroporation delivery devices, have been shown to be safe and
increase immune responses to targeted antigens 100-fold.