Watching tumors burst through a blood vessel

Attacking Cancer Indirectly: Immunity Against Tumor Vessel Protein


April 26, 2014
Health

Sometimes a full-on assault isn’t the best approach when dealing with a powerful enemy. A more effective approach, in the long run, may be to target the support system replenishing the supplies that keep your foe strong and ready for battle.

A group of researchers from the Abramson Cancer Center and the Perelman School of Medicine at the University of Pennsylvania is pursuing this strategy by employing a novel DNA vaccine to kill cancer, not by attacking tumor cells, but targeting the blood vessels that keep them alive. The vaccine also indirectly creates an immune response to the tumor itself, amplifying the attack by a phenomenon called epitope spreading. The results of the study were published this month in the Journal of Clinical Investigation.

Previous studies have targeted tumor angiogenesis (the formation of new blood vessels that feed the tumor cells). However, this approach can also interfere with normal processes involved in wound healing and development. Penn researchers avoided this pitfall by designing a DNA vaccine that specifically targets TEM1 (tumor endothelial marker 1), a protein that is overexpressed in tumors and poorly expressed in normal tissues.

“We demonstrated that by targeting TEM1, our vaccine can decrease tumor vascularization, increase hypoxia of the tumor and reduce tumor growth,” says Andrea Facciabene, PhD, research assistant professor of Obstetrics and Gynecology and a faculty member in the Ovarian Cancer Research Center at Penn Medicine. “Our results confirm that we were directly targeting the tumor vasculature and also indirectly killing tumor cells through epitope spreading.”

The Penn team injected mice with a DNA fusion vaccine called TEM1-TT, created by fusing TEM1 complementary DNA with a fragment of the tetanus toxoid (TT). In mouse models of three cancer types (breast, colon, and cervical), tumor formation was delayed or prevented in mice vaccinated with the TEM1-TT DNA vaccine.  Specifically, they found that the mouse tumors had suppressed growth, decreased tumor vessel formation, and increased infiltration of immune cells into tumors.

The researchers found that the DNA vaccine, after killing the endothelial cells that make up the tumor vessels (vasculature), also resulted in epitope spreading, meaning that the immune cells of the mice gathered pieces of dead tumor cells (due to hypoxia) to create a secondary immune response against the tumor itself. The vaccine induced specific T cells to fight other tumor cells expression other proteins, in addition to TEM1, thus increasing its therapeutic efficacy.

The new DNA vaccine approach to fight cancer is showing great potential compared to previous studies that focused on tumor cells rather than the blood vessels that allow tumor cells to thrive.

“Until now there have been a lot of clinical trials using DNA vaccines to target tumors themselves, but unfortunately the results have been disappointing,” Facciabene notes. “This is a different approach which should heighten optimism for cancer vaccines in general. Moreover, based on what we’ve seen in our mouse studies, this vaccine doesn’t seem to show any significant side effects.”

The prevalence of TEM1 in a wide range of tumor types coupled with its scarcity in normal vessels makes it a suitable target both for a prophylactic defense against cancer and a complement to other therapies such as radiotherapy and chemotherapy. “Using this vaccine simultaneously with radiation may eventually have a double synergy,” Facciabene says. “Both treatments affect the tumor endothelium, radiotherapy could help the phenomenon of epitope spreading induced by the TEM1-TT vaccine.” In addition to ongoing pre-clinical work with human TEM1, Facciabene and colleagues are planning to move on to Phase I human clinical trials.

The authors suggest that TEM1 may also be an excellent target as a prophylactic cancer vaccine for individuals that have a high risk of developing ovarian cancer, such as carriers of the BRCA1/2 mutations, predominant in breast and ovarian cancer. Research to develop those types of strategies is a key goal of Penn’s Basser Research Center for BRCA. As a bonafide vaccine, TEM-TT DNA vaccine generates a memory immune response, which Facciabene says is an ideal attribute for high risk populations.

The research was supported by the Basser Research Center for BRCA, the Alliance for Cancer Gene Therapy, the NIH Director’s New Innovator Award (1DP2OD008514), and the Pennsylvania Department of Health (4100051725).


13 Responses to Attacking Cancer Indirectly: Immunity Against Tumor Vessel Protein

  1. JG Tredoux (14009383) May 2, 2014 at 3:06 am #

    Cancer as always been a credible threat in societies of the world. Thinking of creating a vaccine is beyond comprehension. This is good news for the world! Many people suffer daily with chemo therapy and radiation, both of these treatments having tremendous side effects. And these treatments’ usefulness is questioned sometimes depending on the type of cancer the person has. So obtaining a vaccine or some kind of medicine to help with the treatment or the prevention of diseases are a huge step forward for the medical profession. But even though the trails with the mice seemed to work really well. They must do the human trails with all the approved ethics. Drug companies tend to sometimes think more about the revenue than they do about the actual treatment and side effects the drugs can have. They have to test the TEM1-TT vaccine very well before beginning with distribution. The way the field of medicine is expanding by people thinking outside the box, for example rather attack the source of power of a tumor than the tumor itself, will lead to great accomplishments in the 21 century.

  2. u14028868 May 1, 2014 at 11:37 am #

    This is a very intrigue research!

    Using the TEM-1 cancer vaccine will improve the treatment of cancer and add hope of survival to the victims of cancer.Creating immunity against malignant cells is a great way of permanently treating the lethal cancer disease.

    However,there are cancer therapies that are being researched in an extensive way.Yes,these are going to be beneficial to everyone but i think they pose a hazardous effect to human beings as there are still some uncertainties of giving these therapies to human beings.

    We have to keep up with the times(Medical advancements etc),but,why can’t we stick to the primitive methods of healing cancer as these new methods have a lot of uncertainties ?

  3. 14121124 April 29, 2014 at 1:17 pm #

    The ability to provide protection from tumours, before they even form is an incredible revolutionary step in our battle against cancer. The Tumour Endothelial Marker 1 (TEM1), a protein overexpressed in tumours, is targeted in the blood vessels that keep tumours alive. This could result in the prevention of tumours even forming through a DNA vaccine. A possible medical protection from cancer even forming is unheard of and could change the way we see medicine. If already formed, the cells of the tumour are deprived of oxygen, as well as creating an immune response to the tumour. Through building up an immune response, the possibility of contracting the disease again is greatly reduced, which is a huge benefit of this vaccine.This approach could possibly provide an alternative to chemotherapy and radiation which are known to have harsh side effects and may not always be successful.

    This research however is still in the very early stages; tests on mice provide us with some insight into how we may react to the vaccine however such data can’t be completely relied on as we are two completely different species, with many varying characteristics.

    Many clinical trials will need to be done with humans; these will require extensive test subjects and huge amounts of funding, in order to completely examine if the vaccine works, the viability of this vaccine and whether there are any side effects. There is also the question of cost, if the vaccine proves to be successful; will the vaccine be covered by medical aid? Will it be expensive and unaffordable for the majority of the population? Will it be provided free of charge by public hospitals?

    Non-communicable diseases are on the rise, therefore research into methods of prevention and treatment are increasingly important. Almost everyone has been affected by cancer, directly or indirectly, thus the research into this field is vital. Hopefully TEM1-TT vaccine will be able to change the way we approach and see cancer sometime in the future.

  4. MJ Kgaphola April 29, 2014 at 3:52 am #

    Deaths related to cancer have been increasingly affecting our world.As for cancer that is related to an increased size of tumor, has been making people live a difficult life and eventually most of them died at the end, as it was growing in size in their bodies every time.

    It is a relieve that there is a DNA vaccine that will target the tumor and kill cells indirectly. That way it will reduce the amount of cells causing cancer and reduce the size of tumor.Many people who suffer from this type of cancer will be saved and the coming generation. I wish it would benefit everyone and not just developed population who have access to private hospitals only.

    What I want to know is whether the DNA vaccine will be very expensive in such a way that those who suffers from it will not afford to pay?.If it is the case then we still got a long way to go.But all in all it is such big stepping stone.

  5. u14008859 April 29, 2014 at 2:05 am #

    Cancer accounts for 13% of deaths each year and it is the second leading cause of death in developing countries.Pioneering medical researchers may have just developed the most influential drug with regards to cancer treatment and prevention in the form of the TEM1-TT vaccine.
    I say this because this vaccine is very different to present forms of treatment such as chemo and radiation such that its has few side effects and does not focus on killing tumor cells but targets the tumor vessels (what makes the tumor thrive). This simultaneously reduces tumor growth and creates a secondary immune response against the tumor cells. This immune response reduces the probability of cancerous cells forming else where in the body. This is probably one of the main advantages of TEM11-TT vaccine because with present forms of treatment the remission period is indefinite and patients live in fear of contracting the fatal disease again.
    The fact that the TEM1-TT drug has few side effects will make a significant change in the quality of living for patients undergoing treatment as apposed to chemo patients who fall more ill from the chemo than the cancer itself. This will drastically improve the mental state of the patient as they may no longer view their quality of life as fatal.
    This is a ground-breaking discovery however its long term effects on a patient are still ambiguous as it is a new drug. There are still many questions about it such as how much will it cost? Can patients just have the vaccine only, or do they have to follow a specific diet regime and for how long after they take the vaccine must this continue for?

  6. SB.Mtabela(14098408) April 29, 2014 at 1:22 am #

    I think this way of treating cancerous cells in the body, is much more effective rather than the primitive way of treating the cancer cells which was by only destroying the tumors rather than the host itself that creates the cancer cells in the body

    The use of TEM 1 is a very good mechanism to use; which is used as a prophylactic barrier against cancerous growths in the breasts. It was also a very wise development to establish such a vaccine that had less side effects while destroying those tumors in the cells of the body.

  7. N. Wilson (14070457) April 28, 2014 at 11:46 pm #

    The treatment of cancer has become one of the quickest growing research fields in recent years, due to the huge impact this disease has on our population. It is no wonder new treatments are being discovered on a regular basis.

    Creating alternatives to the currently used forms of treatments, including chemotherapy and radiotherapy, is essential, due to the very well known side effects. This article informs us of a treatment that sounds ideal, as it seems very effective in the fight against cancer cells, yet does not produce the side affects cancer patients know so much about. For one, unlike chemotherapy, the TEM-1 TT vaccine has no effect on fertility of the patient at a later stage. For women, this is a very important advantage, and will probably play a huge role when deciding on a suitable cancer treatment.

    However, despite how flawless this treatment sounds, the readers have not been informed of any or if any side affects exist, even if they are minor, which surely there will be while eliminating cells in your body?

    Alternative treatments should also be examined, such as heat sensitive Lysosomes, which, just like the TEM-1 TT vaccine, is being tried and tested. Of these, the most effective treatment should be decided on, and extensive research should be established in that field to ensure the success of the treatment, and success in saving the lives of many cancer sufferers.

  8. A. Smit (14023190) April 28, 2014 at 9:53 am #

    This vaccine will bring great hope for the cure of cancer for patient who’s cancer cant be surgically removed or for those who don’t want the extreme side-effects from chemo or radio treatment but this vaccine also brings some questions to mind:

    The cost of production and the cost of attaining this vaccine?
    How often does this vaccine have to be administered or is it a once off case?
    How long will it take for dis type of vaccine to pass all the phases so that it can be attained by the public?
    Is this vaccine a better choice over that of nano-bot technology that is currently the new innovation in treating cancer?

  9. 14138982 April 28, 2014 at 12:27 am #

    Malignant tumors cause a great stir of concern and confusion amount those it affects. This TEM1 vaccine is indeed a great alternative to other therapy such as chemotherapy or radiography which show many disturbing side effects. However, while chemotherapy and radiography are ongoing treatments depending on the size and age of the tumor, how often would a cancer patient have to receive this vaccine?

    Cancer treatment is costly, and so now everyone can afford it, and many patients die of cancer. Is this vaccine also expensive? Because if it is, this would mean that yet again the financially disadvantaged will be deprived of good cancer treatment.

  10. Tarn-14052424 April 28, 2014 at 12:14 am #

    The most impressive advantage of the DNA fusion vaccine, TEM1-TTDNA vaccine, is that it is aimed to strengthen the body to fight against cancer- Instead of breaking down and weakening all of the cells with radiation, using chemotherapy, in an attempt to destroy the cancer cells along with the other cells, in which case even if the cancer is cured the patient usually remains sick and vulnerable to other illnesses due to the weakening of their body during treatment. If this vaccine is as successful in the human trial as it was in the mice trial, the DNA vaccine will cure cancer and unlike the others, leave the patients healthier than they were before the cancer. This advantage is the added value over other solutions.

  11. Matt B (14022363) April 27, 2014 at 6:44 am #

    Hearing the words “you have cancer” is what over 12 million people hear each year worldwide and consequently more people die globally from cancer than AIDS, Malaria and TB combined (National Cancer Registry 2005).

    Current cancer treatments such as radiotherapy & chemotherapy may reduce the tumor and surgery can remove it in some instances where it is accessible however this does not guarantee the patient will be fully cured as in many cases the tumor reappears elsewhere in the body.

    This new innovative form of treatment is definitely an example of working smart and not hard to fight the disease. It provides a simple solution to an ever-growing problem where only a single vaccine will be the ultimate cure. What is interesting about this vaccine is it does not only specifically target the blood vessels related to the tumor but it also creates an immune response to the tumor itself. The immune response created can help to prevent further arousal of the cancer tumor elsewhere in the body which often occurs in many cancer patients. Lastly, an added bonus is that the drug is showing no side effects in the trial process which could make cancer treatment less painful and invasive to what it is today.

    The DNA fusion vaccine is a great breakthrough in cancer treatment, hopefully one that succeeds in fighting this increasingly complex disease.

  12. u14052564 April 27, 2014 at 2:49 am #

    Tumours are most often the source of the cancer in a person and in serious cases, a tumour may not always be able to be removed. Even if there is the possibly of removing the tumour, this may not entirely be the cure of the cancer as some cancer cells may remain behind. This is thus not a cure to the cancer pandemic. The vaccination however, will be useful in the treatment and prevention of tumours as it is attacking the direct cause of the tumour. It is especially useful as it is being used to destroy cancerous cells. The vaccination may provide useful insight into developing a potential cure to cancer and a treatment in the fight against cancer.

  13. 14021880- Michelle Morgan April 26, 2014 at 12:45 pm #

    Tumors cannot always be surgically removed due to their size and/or their location. Even when tumors can be surgically removed cancerous cells can spread to other parts of the body by using the victim’s bloodstream as a form of transport to the rest of the body. This vaccination will thus be extremely helpful as it targets a certain protein that is abundant within cancerous cells. The vaccination will kill off all cancerous cells within the body without any risky surgical procedures. This is truly a big step forward within the continuously developing medical field.

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