Plants could act as safe, speedy factories for growing antibodies for
personalized treatments against a common form of cancer, according to new
findings from the Stanford University School of Medicine.
The findings came in the first human tests of an injectable vaccine grown in
genetically engineered plants.

The treatments, which would vaccinate cancer patients against their
malignant cells, could lead to earlier personalized therapy to tackle
follicular B-cell lymphoma, an immune-system malignancy diagnosed in about
16,000 people each year.

Doctors regard follicular B-cell lymphoma as a chronic, incurable disease.
The standard treatment, chemotherapy, has such severe side effects that
patients often opt for watchful waiting in the early stages of illness.
However, plant-grown vaccines, which lack side effects, could allow earlier,
more aggressive management of the cancer.

?This would be a way to treat cancer without side effects,? said Ronald
Levy, MD, professor of oncology and the Robert K. and Helen K. Summy
Professor in the School of Medicine, who is the study?s senior author. ?The
idea is to marshal the body?s own immune system to fight cancer.?

The findings will appear July 21 in the advance online issue of the
Proceedings of the National Academy of Science. The study was a phase-1
trial that showed plant-grown cancer vaccines were safe for patients and
could be produced quickly and cheaply. Sixteen newly diagnosed lymphoma
patients received the treatment; none experienced any side effects from
plant-grown vaccines.

Future studies will test the vaccine?s effectiveness.

The cancer vaccines rely on a biological quirk of follicular B-cell
lymphoma, which is a type of non-Hodgkin?s lymphoma. The cancer starts when
a single immune cell multiplies uncontrollably, producing many identical
clones of itself. The clones all carry the same antibody on their exterior,
a marker that is unique to the cancer and is not found on any of the body?s
healthy cells. Levy?s vaccination strategy is to inject many copies of the
cancer-specific antibody into a newly diagnosed lymphoma patient,
stimulating the patient?s immune system to seek and destroy malignant cells.

Previous trials of this kind of vaccine, produced in animal cells and tested
in mice and humans, have had mixed success, and the vaccines are not yet
commercially available. Growing cancer vaccines in plants could circumvent
some of the hurdles to turning the concept into a real treatment, Levy said.

Because each person?s cancer antibody is unique, every patient needs a
personalized vaccine. Growing personalized vaccines in animal cells takes
months, costs thousands of dollars per patient and comes with the
theoretical risk that a patient might inadvertently be infected with an
animal virus that contaminated the cells used to grow the vaccine.
Personalized vaccines could also be produced with genetically engineered
bacteria, but bacteria-grown vaccines aren?t ideal, either.

?The plant system has some advantages,? said Levy, who is also a member of
the Stanford Cancer Center and a Howard Hughes Medical Institute
investigator.

The researchers chose tobacco plants that were genetically engineered to
reproduce quantities of the vaccine. To make a tobacco plant churn out a
human antibody, scientists isolate the antibody from the patient?s tumor and
put the antibody gene into a modified version of the tobacco mosaic virus.
They infect a tobacco plant with the gene-carrying virus by scratching the
virus on its leaves. The virus takes the gene into the plant?s cells, which
then churn out lots of antibody. After a few days, technicians snip off the
plant?s leaves, grind them up and purify the antibody. Only a few plants are
needed to make enough vaccine for each patient.

?The new manufacturing system allows very rapid production of a vaccine,?
said Charles Arntzen, PhD, a professor of plant biology at the Arizona
Biodesign Institute at Arizona State University, who was not involved in the
research. ?I think without the speed, it would be hard to convince a cancer
patient to wait for a vaccine to be developed, rather than going on some
other therapy.?

?It?s pretty cool technology,? Levy said. ?And it?s really ironic that you
would make a treatment for cancer out of tobacco. That appealed to me.? None
of the harmful chemicals found in cigarettes end up in the purified
vaccines.

Not only is the technology fast, cheap and safe, but Levy said there?s
reason to expect that the plant-grown antibodies will generate a stronger
immune response than those made in animal cells. Both plant and animal cells
attach sugars to antibodies and other proteins during biochemical
processing, but the plant and animal sugars are different. The difference
might prompt a more robust immune response to plant-grown antibodies, Levy
said.

The next research step is a phase-2 clinical trial to test the effectiveness
of plant-grown vaccines in a larger group of lymphoma patients, Levy said.
He?s optimistic, adding, ?We know that if you get the immune system revved
up, it can attack and kill cancer.?

The research team included scientists from Stanford, Touro University in
Vallejo, Calif., and the biotechnology companies Large Scale Biology Corp.,
CBR International Corp., Bayer HealthCare, Integrated Biomolecule Corp., The
Biologics Consulting Group Inc. and Holtz Biopharma Consulting.

The study was funded by a grant from the National Institutes of Health and
by Large Scale Biology Corp.

About Stanford University Medical Center
Stanford University Medical Center integrates research, medical education
and patient care at its three institutions - Stanford University School of
Medicine, Stanford Hospital & Clinics and Lucile Packard Children?s Hospital
at Stanford. For more information, please visit the Web site of the medical
center?s Office of Communication & Public Affairs at
[mednews.stanford.edu].
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