Abstract: An isolated binding partner of a Cripto-1 protein, Pim-1 protein or
an antigen present in a colon cancer cell lysate is described. The binding
partner inhibits growth of one or more cancer cell types and may be used in an
anti-cancer agent for treating cancer in a subject. The binding partner may
also be used in a method of inducing apoptosis in a cancer cell, as well as in
a method of sensitizing a cancer cell to a cytotoxic compound. In addition, a
cancer vaccine is described wherein the vaccine comprises a Cripto-1 protein
(or an antigenic fragment thereof), Pim-1 protein (or an antigenic fragment
thereof) or an antigen present in a colon cancer cell lysate or, alternatively,
comprises an expressible DNA molecule encoding a Cripto-1 protein (or an
antigenic fragment thereof), Pim-1 protein (or an antigenic fragment thereof)
or an antigen present in a colon cancer cell lysate. ... http://images2.freshpatents.com/pdf/US20090123470A1.pdf
Shark versus cancer
How Jaws could lend a helping hand in the fight against cancer
By Kelly O'Connor
A breakthrough announcement made recently by a team of researches at La Trobe University in Australia, indicates that antibodies from shark blood could be the next leap forward in cancer treatment. Dr. Stewart Nuttall, one of the lead research scientists for the project, explains it this way: “We're initially interested in sharks because they play a pivotal role in immune evolution. If you look at a shark, anything below them in an invertebrate scale doesn't have an immune system. Sharks and everything above it has an immune system very much like humans. But they also have this unusual type of antibodies.”Shark antibodies are somewhat unusual because of their ability to withstand extreme temperatures, pH levels, and their tiny size; researchers are excited about this because it opens up the possibility of having a pill treatment for cancer rather than having to rely on injections.
Thus far, the major stumbling block with developing an oral treatment for cancer has been the harsh environment of the digestive system. Mick Foley, associate professor of molecular biology at La Trobe University and co-lead researcher, describes the difficulties: “The first step in being able to get an orally available antibody, which really is a bit of a holy grail in therapeutics, is to at least survive the gut. And then you have to get it taken up. And so these molecules seem to be extremely stable in the gut. And therefore there is a good chance that we have at least have got past first base.”
If the antibody survives the inhospitable environment of the digestive system, it then binds on to the surface of the target cancer cells and prevents them from growing. There have already been some promising results from the lab, where the researchers have been testing the efficacy of the shark antibody treatment on breast cancer cells. Dr. Foley describes the results: “In the wells that we've added the shark antibodies you can see that the cells are actually growing less than in the wells where we don't add a shark antibody or we add a completely irrelevant shark antibody.
So this indicates the shark antibody that we have is binding to those cancer cells and for some reason causing them to grow more slowly and perhaps even killing them.”
In order to produce such antibodies, the traditional approach has been to inject sharks with an antigen and wait for a sufficient immune response to develop. Instead, these Australian researchers take genes from the sharks, and modify them in the lab by adding random proteins to cause random mutations in a process which closely mimics how the human immune system works.
This enables the researchers to develop a “library” of antibodies capable of responding to a vast array of diseases and conditions, including malaria and rheumatoid arthritis. Dr. Foley explains: “The aim is to use these shark antibodies as a way of finding high-affinity binding agents to bind to anything we want – such as a molecule on cancer cells, or inflammatory proteins that you could then use in therapy.” Through a slow process of trial and error, the researchers expose antibodies to various target molecules (such as cancer cells), and see if there is any reaction. Dr. Foley summarizes the process: “There is maybe a little bit of gold in there, there's a lot of rubbish, and you have to via a very slow process get rid of the rubbish and make sure that the gold is left. So we do that. We sort of put the library on the target molecule and then wash everything away and then we get back what is important, then we amplify that up and then do it again. And we keep doing it until slowly we get the right ones that come out.”
The advantages (and potential payout) of successfully developing an oral-based antibody treatment for cancer are huge. For patients who must be subjected to constant injections, taking pills would be a dramatic improvement. Antibody-based treatments are also much more specific than the current methods. Although there are already other similar treatments in development, they are all in their early stages with none available for patient use as of yet. This leaves a market potentially worth billions of dollars wide open. So next time you see a shark, try to look past those vicious teeth and occasional man-eating tendencies and just appreciate the irony; one of the newest advances in cancer treatment could come from one of the ocean’s most ancient predators.
How Jaws could lend a helping hand in the fight against cancer
By Kelly O'Connor
A breakthrough announcement made recently by a team of researches at La Trobe University in Australia, indicates that antibodies from shark blood could be the next leap forward in cancer treatment. Dr. Stewart Nuttall, one of the lead research scientists for the project, explains it this way: “We're initially interested in sharks because they play a pivotal role in immune evolution. If you look at a shark, anything below them in an invertebrate scale doesn't have an immune system. Sharks and everything above it has an immune system very much like humans. But they also have this unusual type of antibodies.”Shark antibodies are somewhat unusual because of their ability to withstand extreme temperatures, pH levels, and their tiny size; researchers are excited about this because it opens up the possibility of having a pill treatment for cancer rather than having to rely on injections.
Thus far, the major stumbling block with developing an oral treatment for cancer has been the harsh environment of the digestive system. Mick Foley, associate professor of molecular biology at La Trobe University and co-lead researcher, describes the difficulties: “The first step in being able to get an orally available antibody, which really is a bit of a holy grail in therapeutics, is to at least survive the gut. And then you have to get it taken up. And so these molecules seem to be extremely stable in the gut. And therefore there is a good chance that we have at least have got past first base.”
If the antibody survives the inhospitable environment of the digestive system, it then binds on to the surface of the target cancer cells and prevents them from growing. There have already been some promising results from the lab, where the researchers have been testing the efficacy of the shark antibody treatment on breast cancer cells. Dr. Foley describes the results: “In the wells that we've added the shark antibodies you can see that the cells are actually growing less than in the wells where we don't add a shark antibody or we add a completely irrelevant shark antibody.
So this indicates the shark antibody that we have is binding to those cancer cells and for some reason causing them to grow more slowly and perhaps even killing them.”
In order to produce such antibodies, the traditional approach has been to inject sharks with an antigen and wait for a sufficient immune response to develop. Instead, these Australian researchers take genes from the sharks, and modify them in the lab by adding random proteins to cause random mutations in a process which closely mimics how the human immune system works.
This enables the researchers to develop a “library” of antibodies capable of responding to a vast array of diseases and conditions, including malaria and rheumatoid arthritis. Dr. Foley explains: “The aim is to use these shark antibodies as a way of finding high-affinity binding agents to bind to anything we want – such as a molecule on cancer cells, or inflammatory proteins that you could then use in therapy.” Through a slow process of trial and error, the researchers expose antibodies to various target molecules (such as cancer cells), and see if there is any reaction. Dr. Foley summarizes the process: “There is maybe a little bit of gold in there, there's a lot of rubbish, and you have to via a very slow process get rid of the rubbish and make sure that the gold is left. So we do that. We sort of put the library on the target molecule and then wash everything away and then we get back what is important, then we amplify that up and then do it again. And we keep doing it until slowly we get the right ones that come out.”
The advantages (and potential payout) of successfully developing an oral-based antibody treatment for cancer are huge. For patients who must be subjected to constant injections, taking pills would be a dramatic improvement. Antibody-based treatments are also much more specific than the current methods. Although there are already other similar treatments in development, they are all in their early stages with none available for patient use as of yet. This leaves a market potentially worth billions of dollars wide open. So next time you see a shark, try to look past those vicious teeth and occasional man-eating tendencies and just appreciate the irony; one of the newest advances in cancer treatment could come from one of the ocean’s most ancient predators.
This page tells you
about the immune system. There is information on
What your immune system does
The immune system
protects the body against infection caused by bacteria, viruses, fungi or
parasites. It is really a collection of reactions and responses that the body
makes to infection. So it is sometimes called the 'immune response'.
The immune system is
important to cancer patients in many ways because
·
The cancer can weaken the immune system
·
Cancer treatment can weaken the immune system
·
The immune system may help to fight your
cancer
Cancer can weaken the
immune system by spreading into the bone marrow where the cells that help fight
infection are made. This happens most often in leukaemia or lymphoma. But it
can happen with other cancers too. The cancer in the bone marrow stops the bone
marrow making so many blood cells.
Chemotherapy and
radiotherapy can weaken immunity by causing a drop in the number of white blood
cells made in the bone marrow. Apart from bone
marrow transplants or stem cell transplants, this effect on the bone marrow
is temporary. High doses of steroids
can also weaken your immune system temporarily.
Some cells of the immune
system can recognise cancer cells as abnormal and kill them. Unfortunately,
this is not enough to get rid of a cancer altogether. But some new treatments
aim to use the immune system to fight cancer.
There are two main parts
of the immune system
·
The inbuilt
protection we have from birth
·
The
immune protection we develop from being exposed to certain diseases
In-built immune protection
This is also called
'innate immunity'. These immune mechanisms are always ready and prepared to
defend the body from infection. They can act immediately (or very quickly).
This in-built protection comes from
·
A barrier formed by the skin outside the body
·
Inner linings of the gut and lungs which
produce mucus and trap invading bacteria
·
Hairs which move the mucus and trapped
bacteria out of the lungs
·
Stomach acid which kills bacteria that have
been swallowed
·
Helpful bacteria growing in the bowel which
prevent other bacteria from taking over
·
Urine flow which flushes bacteria out of the
bladder and urethra
·
White blood cells called 'neutrophils' which
can find and kill bacteria and other infectious organisms
The skin forms a
waterproof mechanical barrier. But it is also slightly acidic. This helps to
keep bacteria out as they don't like acid. Some skin conditions cause loss of
this acidity and people are then much more prone to skin infections.
There are several ways
that these natural protection mechanisms can be damaged or overcome if you have
cancer. For example
·
Something may break the skin barrier (such as
having a drip in your arm or a wound from surgery)
·
Chemotherapy may damage to the lining of the
gut (severe diarrhoea caused by some chemotherapy drugs can break down the gut
lining)
·
A catheter into your bladder can become a
route for bacteria to get inside the bladder and cause infection
·
Radiotherapy to the lung can damage the hairs
and mucus producing cells that help to remove bacteria
·
Antacids for heartburn may neutralise the
stomach acid that kills bacteria
·
Chemotherapy can temporarily reduce the
number of neutrophils in the blood (the 'neutrophil count') which means it is
more difficult for you to fight off infection
Neutrophils
These white
blood cells are very important for fighting infection. They can
·
Move to areas of infection in the body
·
Stick to invading bacteria or fungi
·
Swallow up the bacteria, viruses or fungi
causing the infection
·
Kill the bacteria they have swallowed with
chemicals
Your normal neutrophil
count is between 2,000 and 7,500 per cubic millimetre of blood. When you don't
have enough neutrophils you are said to be 'neutropaenic'.
Chemotherapy and some
radiotherapy treatments can lower your neutrophil count. So, after chemotherapy
or radiotherapy you may be more likely to get bacterial or fungal infections
(like thrush).
If you are having cancer
treatment, it is important for you to know that
·
Infections can become serious more quickly in
people with low neutrophil counts
·
Antibiotics could save your life, so if you
get a fever or feel ill, phone your cancer centre or go to casualty (Accident
and Emergency) straight away
You are most likely to
become ill from bugs you carry around with you normally, not from catching
someone else's. This means that you don't have to avoid your family, friends or
children when you are sent home after chemotherapy.
You can ask your cancer
doctor or nurse what precautions you should take against infection. There are
also some tips in our cancer
drug side effects section.
When your blood counts
are low, your cancer specialist may want you to take antibiotics to help
prevent severe infection. There is some debate about whether this is useful. In
the
Significant Trial, some people had an antibiotics during treatment and some
had a dummy tablet (placebo). The results showed that fewer people who had
antibiotics during treatment had a fever or had to go to hospital for treatment
for an infection.
Acquired immunity
This is immune
protection the body learns from being exposed to diseases. The body learns to
recognise each different kind of bacteria and virus it meets for the first time.
The next time that particular bug tries to invade the body, the immune system
is ready for it and able to fight it off more easily. This is why you usually
only get some infectious diseases once - for example, measles or chicken pox.
Vaccination works by
using this 'immune memory'. The vaccine contains a small amount of protein from
a disease. This is not harmful, but it allows the immune system to recognise
the disease if it meets it again. The immune response can then stop you getting
the disease. Some vaccines use tiny amounts of the live bacteria or virus.
These are called live attenuated vaccines.
Attenuated means that the virus or bacteria has been changed so that it will
stimulate the immune system to make antibodies but won't cause the infection.
Other types of vaccine use killed bacteria or viruses, or chemicals produced by
bacteria and viruses.
B cells and T cells
The white blood cells
involved in the acquired immune response are called 'lymphocytes'. There are
two main types of lymphocytes - B cells and T cells. B and T lymphocytes are
made in the bone marrow, like the other blood cells. They have to fully mature
before they can help in the immune response. B cells mature in the bone marrow.
But the immature T cells travel through the blood stream to the thymus
gland where they become fully developed.
Once they are fully
mature, the B and T cells travel to the spleen and lymph
nodes ready to fight infection.
What B cells do
B cells react against
invading bacteria or viruses by making proteins called antibodies.
The antibody made is different for each different type of bug. The antibody
locks onto the surface of the invading bacteria or virus. The invader is then
marked with the antibody so that the body knows it is dangerous and it can be
killed off. Antibodies can also detect (and kill) damaged cells.
The B cells are part of
the memory of the immune system. The next time the same bug tries to invade,
the B cells that make the right antibody are ready for it. They are able to
make their antibody very quickly.
What antibodies are
Antibodies are proteins
made by the B
cells. They have two ends. One end sticks to proteins on the outside of
white blood cells. The other end sticks to the germ (or damaged cell) and helps
to kill it. The end of the antibody that sticks to the white blood cell is
always the same. So it is called the constant end. The end of the antibody that
recognises germs and damaged cells varies depending on the cell it is designed
to recognise. So it is called the variable end. Each B cell makes antibodies
with a different variable end from other B cells. Cancer cells are not normal
cells. So some antibodies with variable ends recognise cancer cells and stick
to them.
What T cells do
There are different
kinds of T cells called
·
Helper T cells
·
Killer T cells
The helper T cells
stimulate the B cells to make antibodies, and help killer cells develop.
Killer T cells kill the body's
own cells that have been invaded by the viruses or bacteria. This prevents the
bug from reproducing in the cell and then infecting other cells.
Can the immune system cure cancer?
Your immune system is
very unlikely to be able to fight off an established cancer completely without
help from conventional cancer treatment, although there are very rare
documented cases of cancers just disappearing (spontaneous regression). Some
treatments use elements of the immune system to help treat cancer.
Immunotherapy
Immunotherapy is a type
of biological
therapy. Biological therapies use natural body substances or drugs made
from natural body substances to treat cancer. Immunotherapies
are treatments that use your immune system. They are used in cancer treatment
because cancer cells are different from normal cells and so can be picked up by
the immune system.
Many different chemicals
that are produced as part of the immune response can now be made in the
laboratory. You may have heard of one or two of these
Interferon-alpha and
Interleukin 2 act by boosting the immune response to help the body kill off
cancer cells.
Scientists are also
trying to develop vaccinations
against cancer cells. It may be possible for them to help the immune system
to be trained to see cancer cells as being invaders and kill them.
Monoclonal antibodies
Monoclonal
antibodies are made in the laboratory. The scientists developing them make
an antibody with a variable end that recognises cancer cells. 'Monoclonal' just
means that all the antibodies are exactly the same type, with the same variable
end.
The monoclonal
antibodies recognise molecules on the outside of cancer cells. Different
antibodies have to be made for different types of cancer, for example
·
Rituximab
(Mabthera) recognises CD20 protein on the outside of some lymphoma cells
·
Bevacizumab
(Avastin) targets growth factors that help blood vessels grow and is used
to treat bowel cancer and breast cancer
·
Trastuzumab
(Herceptin) recognises breast cancer cells that produce too much of the
protein HER 2 - these cancers are called HER 2 positive
The constant end of
cancer treating monoclonal antibodies kills the cancer cells by marking them so
other immune system cells pick them out. The job of these other cells is to
find antibody labelled cells and kill them. But the scientists can make the
monoclonal antibody even better at killing cancer cells by attaching
·
A radioactive atom that delivers radiation
directly to the cancer cells
·
A chemotherapy drug that is taken straight to
the cancer cells by the monoclonal antibody
Monoclonal antibodies
are still being researched but are now used for more and more types of cancer.
Look in our clinical
trials database for monoclonal antibody trials - type 'antibody' into the
free text search box. This is an exciting new area of cancer treatment. There
is a lot of research going on into the use of immune system therapies to treat
cancers. There is detailed information about this in the biological
therapies section of CancerHelp UK. You can also look in the treatment
section of the type
of cancer you are interested in.
Stress, the immune system and cancer
Many people with cancer
believe that they should strengthen their immune systems to help beat the
disease. There is a commonly held belief that reducing stress can help to
strengthen our immune systems. This is the thinking behind some complementary
therapies, using relaxation techniques for instance.
There is some scientific
evidence that stress weakens our immunity. Two studies looking at whether
stress affected cancer recurrence had conflicting results. While no one knows
whether strengthening immunity can help to cure cancer, most doctors and nurses
agree that reducing stress is a good thing to do.
While many life stresses
cannot be avoided altogether, there are ways of trying not to let things get to
you. Many complementary
therapies such as meditation,
massage
and reflexology,
can be very relaxing.
You can avoid getting
run down and look after yourself by
·
Eating a balanced diet when you are able
·
Trying to eat fresh food whenever possible
·
Getting plenty of rest - even if you find it
hard to sleep, you can rest
In ovarian cancer, the lethal cancer cells get accumulated in the ovaries. Since ovaries are important for producing eggs for reproduction, this deadly disease affects the female reproductive and sexual organs. Different types of tumor cells like stromal, germ cell and epithelial tumors cause this type of cancer.
A lot of research has gone into fighting the numerous cancer cells that affect the individuals. With all treatments and medications, scientists find it a challenge to treat this disease.
Lately, a new antibody has been found by the researchers in order to fight against the cancer cells that attack the immune system of the body. This has offered new hopes for treating ovarian cancer among women.
This antibody named AD5-10 attaches to the cancer cells weakening the resistance of the tumor cells to the body's immune system. In addition, this antibody is found to be more effective for chemotherapy.
AD5-10 antibody decreases resistance of the cells to carboplatin, a common agent used in chemotherapy. The combined effect of this antibody along with carboplatin was more effective for treating cancer patients. Reports also revealed that the antibody is found to react in this manner only when the cell killers known as lymphocytes NK are present in the tumor cells during the same time.
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http://www.pnl.gov/news/release.aspx?id=796 Silica cages help anti-cancer antibodies kill
tumors in mice
RICHLAND, Washington – Packaging anti-cancer drugs into particles of
chemically modified silica improve the drugs' ability to fight skin cancer in
mice, according to new research. Results published May 3 in the Journal of
the American Chemical Society online show the honeycombed particles can
help anti-cancer antibodies prevent tumor growth and prolong the lives of mice.
"We are very excited by our preliminary
results," said biochemist Chenghong Lei of the Department of Energy's
Pacific Northwest National Laboratory, part of the team of PNNL and University
of Washington scientists. "We plan to do some additional, larger studies
with animals. We hope the results hold up well enough to take it to clinical
trials somewhere down the road."
Anti-cancer antibodies are some of the most
promising types of cancer therapies. The antibodies target a particular protein
on cancer cells and — in a poorly understood way — kill off the cells. Examples
include herceptin for one form of breast cancer and cetuximab for colon cancer.
Unlike popping a pill, however, antibody-based
treatments require patients to go in for intravenous drips into the arm. These
sessions cost time and money, and expose healthy tissue to the antibody,
causing side effects.
Packaging antibodies into particles would concentrate
them at the tumor and possibly reduce side effects. Other research has shown
silicon to be well tolerated by cells, animals and people. So, in collaboration
with tumor biologist Karl Erik Hellstrom's group at UW, the scientists explored
particles made from material called mesoporous silica against cancer in mice.
"The silica's mesoporous nature provides
honeycomb-like structures that can pack lots of individual drug
molecules," said PNNL material scientist Jun Liu. "We've been
exploring the material for our energy and environmental problems, but it seemed
like a natural fit for drug delivery."
In previous work, the team created particles that
contain nano-sized hexagonal pores that hold antibodies, enzymes or other
proteins. In addition, adorning the silica pores with small chemical groups
helps trap proteins inside. But not permanently — these proteins slowly leak
out like a time-release capsule.
The researchers wanted to test whether anti-cancer
antibodies packaged in modified mesoporous silica would be more effective
against tumors than free-flowing antibodies.
To do so, they first chemically modified mesoporous
silica particles of about six to 12 micrometers (about 1/10 the diameter of
human hair). These particles contained pores of about 30 nanometers in
diameter. They found that the extent and choice of chemical modification —
amine, carboxylic acid or sulfonic acid groups — determined how fast the
antibodies leaked out, a property that can be exploited to fine tune particles
to different drugs.
Additional biochemical tests showed that the
antibodies released from the silica cages appeared to be structurally sound and
worked properly.
They then tested the particles in mouse tumors at
UW, filling them with an antibody called anti-CTLA4 that fights many cancers,
including melanoma, a skin cancer. The team injected these packaged antibodies
into mouse tumors. The team also injected antibodies alone or empty particles
in other mouse tumors.
The packaged antibodies slowed the growth of tumors
the best. Treatment started when tumors were about 27 cubic millimeters.
Untreated tumors grew to 200 cubic millimeters about 5 days post-treatment.
Tumors treated with antibodies alone reached 200 cubic millimeters on day 9,
showing that antibodies do slow tumor growth. But tumors treated with packaged
antibodies didn't reach 200 cubic millimeters until day 30, a significant
improvement over antibodies alone.
The team repeated the experiment and found the
treatment also prolonged the lives of diseased mice. Of five mice that had been
treated with particles alone, all died within 21 days after treatment. But of
five mice treated with the packaged antibodies, three were still alive at 21
days, and two at 34 days, when the experiment ended.
The team also measured how much antibody remained
in the tumors. Two and four days after injection, the researchers found
significantly more antibody in tumors when the antibodies had been encased in
the silica particles than when the antibodies had been injected alone.
The team is testing other antibody-cancer pairs in
mice, especially other cancers that form solid tumors such as breast cancer.
They are also going to explore how the antibodies delivered this way induce the
immune system to better fight cancer.
"We want to understand the mechanism, because
not much is known about how the slowly leaked antibodies induce changes in the
immune system or in the micro-environment of the tumor," said Hellstrom.
Reference: Chenghong Lei, Pu Liu, Baowei
Chen, Yumeng Mao, Heather Engelmann, Yongsoon Shin, Jade Jaffar, Ingegerd
Hellstrom, Jun Liu, Karl Erik Hellstrom, Local release of highly loaded
antibodies from functionalized nanoporous support for cancer immunotherapy, May
3, 2010 J. Am. Chem.
Soc., DOI 10.1021/ja102414t (http://pubs.acs.org/doi/full/10.1021/ja102414t).
This work was supported by PNNL, Washington Research Foundation, UW Institute
of Translational Health Sciences, the NIH, and the U.S. Department of Energy
Office of Basic Energy Sciences in the Office of Science.
UW Medicine includes the School of Medicine, Harborview
Medical Center, UW Medical Center, Northwest Hospital & Medical Center, UW
Medicine Neighborhood Clinics, UW Physicians, Airlift Northwest, and the UW's
involvement in the Seattle Cancer Care Alliance. UW Medicine has major academic
and service affiliations with Seattle Children's Hospital, Fred Hutchinson
Cancer Research Center, and the Veteran's Affairs Puget Sound Health Care
System in Seattle and VA Hospital in Boise. The UW School of Medicine is the
top public institution in federal funding for biomedical research. Follow us on Twitter -
@UWMedicineNews
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