Tuesday, 1 April 2014

Cancer Vaccine AV0113: “Spindly armed teacher” fights cancer with craftiness and a hint of stamina - New developments in immunotherapy

Immunotherapy - Fight tumours with your own cells

cancer immunotherapy - dendritic cells - attacking tumors glioblastoma - colon cancer - lung cancer - prostate cancer - liver cancer
Diagram demonstrating the protocol and concept of a new and FDA 
approved cancer immunotherapy called AV 0113 from Activartis. 
This cancer treatment is referred to as a completely individualised 
cancer immunotherapy based on dendritic cells (DC)
.
Most people don’t have a doppelganger or evil twin, i.e. most people are unique. Similarly, no two cancers are exactly the same. Even patients who have the “same” type of cancer (e.g. colon cancer) will find that the colon cancer they have is unique and not identical to any other patient with the same disease. In other words tumours are very heterogeneous. As a consequence, some therapies work very well for some cancer patients, while for other patients the same drug or therapy does not have any effect.  Given that in many cases patients will experience recurrence of a tumour after surgical removal (i.e. cancer coming back), personalised immunotherapy to prevent such recurring tumour growth or metastasis may well be the only option to bring about complete tumour regression without toxic side effects for the patient. 

The concept of personalised immunotherapy is as simple as it is elegant. Re-programming the immune system by targeting the master cells that initiate, control and modulate the effector cells of the immune system is the aim of such therapies. The master cells that control and “educate” the immune system are called Dendritic Cells (DCs). The characteristically spindly branch-like appearance of DCs, gave the discoverer (Dr Ralph Steinman) the idea to call them dendritic cells (dendritic means having a branched form that resembles a tree). By expanding, guiding and activating those DCs, it is thought that the overall immune system can be re-set to recognise and attack tumour cells. 

Treatment strategies for cancer patients

For info about Biozantium by Paeon Laboratories:  http://www.biozantium.com
Unfortunately, the adoption of cancer immunotherapy by mainstream standard cancer care hospitals has been slow. Often the medical establishment has religiously subscribed to treating cancer patients with chemo- and radio-therapy whilst pro-actively snubbing the promising field of molecular cancer immunotherapy. As such, cancer immunotherapy is still viewed by many physicians as an experimental concept, despite the vast amount of evidence that clearly indicates that cancer immunotherapy is superior, safer, and less costly compared to any other cancer treatment. Given these parameters, and the time it takes to educate and convince physicians of the benefit of cancer immunotherapy, it is unlikely that immunotherapy will replace any standard chemotherapy treatment in the near future for the vast majority of patients. Also, please note that the new cancer immunotherapy treatment schedules which do get introduced into cancer centres are often obliged to accommodate the current first line standard treatments (in common cancer care settings as well as clinical trials).  

Mainstream standard cancer care with Cancer immunotherapy as an add-on treatment

Typically, first line cancer treatment consists of surgical removal of a primary tumor (when operable), followed by various combinations of chemotherapy and / or radio therapy. Sadly, chemotherapy usually results in damage to the immune system (as well as other tissues and organs in the body) as a side effect.
Hence, when treatment schedules for new cancer immunotherapies are designed, a balance needs to be struck between the ideal scenario of early therapeutic intervention (i.e. immediately after diagnosis) or during / after chemo therapy (i.e. when all else has failed and your immune system has been damaged).

How does AV0113 (Activartis) work?

The patented Activartis AV0113 therapy is a completely individualised cancer immunotherapy which uses the patient’s own dendritic cells (DC) as depicted in the diagram above. A relatively small amount of white blood cells (called monocytes, which are the pre-cursors of DCs), is taken from the patient. Normally (in a healthy individual) DCs infiltrate all organs and tissues within the human body. By default these “guarding” cells essentially form a dense network of sensors in the body and scan the cellular environment in order to maintain tolerance for harmless antigens (such as proteins produced by your own cells (i.e. to prevent you from developing auto-immunity)). However, upon coming across an infection or other danger signals, these DCs rapidly switch from their default setting to a potent immune stimulatory setting.

How do resting Dendritic Cells (DCs) manage to switch their default setting?

DCs determine how dangerous an invading pathogen is (or anything else they come in contact with) by analysing specific molecular structures that make up a microorganism through Pathogen-Associated Molecular Patterns (PAMPs) and via endogenous factors such as cytokines and chemokines, that are produced by other surrounding cells in response to an infection or damage. However, direct activation of DCs by PAMPs is crucial for the induction of a primary T cell response. Direct recognition of PAMPs is mediated by Pattern Recognition Receptors (PRR) such as Toll-Like Receptors (TLR) and C-type Lectin Receptors (CLR). An example of a PAMP is LipoPolySaccharide (LPS), which is a component of bacterial cell walls. LPS mediated danger signals cause DCs to move to regional lympnodes (e.g. located in the groin, the neck, etc…). Here, activated DCs present antigens they have picked up in their environment (e.g. an infected part of the body) to T cells whilst they simultaneously release cytokines such as InterLeukin-12 (IL-12). It is this combination of presented danger signals and cytokines that sends T cells on a mission to kill the offending microorganism as well as any infected host cells.

Cancer cells do not release danger signals

Because malignant tumour cells originate from your own cells they do not release danger signals such as PAMPs that can be recognised by danger receptors. As a consequence tumours are not recognised by the DCs of the host immune system. The trouble with DCs that do not have engaged danger receptors is that they actively suppress immune responses, and as such they protect tumours from T cell mediated attacks.

Can we trick Dendritic Cells (DCs) into perceiving tumours as dangerous?

Yes, we can trick DCs into perceiving tumours as dangerous. The basic principle of DC cancer immunotherapy is based on ‘deceiving’ your own Dendritic Cells by exposing them to bacterial danger signals (e.g. LPS) in addition to your own tumour antigens. The foundation for AV0113 (Activartis) and other Dendritic Cell cancer vaccine techniques was laid by Dr William Coley. Dr William Coley had great success with his vaccine and achieved long term durable remissions (of more than 40%) in patients with various types of inoperable metastatic end stage cancers (essentially curing cancer patients). This technique of simultaneously exposing dendritic cells to bacterial danger signals as well as tumour antigens (molecules from your tumour that can cause a weak immune response), forces DCs to categorise the tumour antigens as dangerous.
Road sign indicating DANGER 
As mentioned earlier, this technique of simultaneous exposure relies on taking monocytes from the patient’s blood, and convert them into DCs in a sterile laboratory facility (i.e. outside of the patient’s body). Then, these DCs are combined with fragments of the tumour that was removed during surgery, microbial danger molecules (e.g. LPS) and cytokines. The DCs absorb those tumour fragments and present parts of these tumour cell fragments on their surface (analogous to road warning signs). The “educated” DCs that display these signs on their surface are then injected back into the cancer patient’s body (usually into lymphnodes), where these signs on the surface of DCs then serve to notify other parts of the patient’s immune system (such as cytotoxic CD8+ T cells, B cells that make antibodies, etc...) that any tumour cells with features that resemble the signs which are displayed on the DCs should be attacked. 
In essence the immune system is taught how to distinguish malignant cancer cells from normal cells. This process of vaccination is akin to how immunisation against the flu educates your immune system how to recognise and attack the flu virus. The difference is that, in the case of dendritic cell (DC) immunotherapy, this immune system “education” process occurs partially outside of the patient’s body in a laboratory.

Advantages of immunotherapy over chemo or radiation therapy

Immune therapies, such as AV0113 are far more precise than conventional chemo therapeutic drugs because they can actually distinguish a malignant cancer cell from a healthy one. In addition, this form of therapy enhances a cancer patient’s innate cancer fighting ability as part of a natural process, while it does not rely on toxic compounds (i.e. chemotherapy). The benefit of such an immunotherapy is that the patient has a good chance of complete remission while he or she is unlikely to experience any side effects. Generally speaking, patients that chose to have such a therapy administered do not become ill, and they don’t suffer from hair loss. In fact patients can simply go on with their normal daily lives. However, this form of immune therapy is not a substitute for surgery, but is instead a complementary form of cancer treatment.

Where can you get access to AV0113?

The company Activartis (based in Austria) lists the following hospitals that are taking part in a clinical trial in which the AV0113 therapy is used to treat Glioblastoma Multiforme (GBM).
  1. Medizinische Universität Wien
  2. Medizinische Universität Graz
  3. Medizinische Universität Innsbruck
  4. Krankenanstalt Rudolfstiftung, Wien
  5. Kaiser Franz-Josef Spital, Wien
  6. Donauspital, Wien
  7. Landeskrankenhaus Feldkirch
  8. Salzburger Landesklinikum
The EudraCT number for this trial is: 2009-015979-27. Further details in the European Clinical Trial database can be obtained here.


In case you would like to seek direct contact with this biotech company, please see below the Activartis contact details:

Activartis Biotech GmbH
Zimmermannplatz 10
1090 Vienna, Austria
Phone: +43 1 40470-64084
Email: office@activartis.com

Pharmaceutical companies interested in a partnership with Activartis should contact Douglas Lloyd-Fell to discuss potential opportunities such as setting up a Phase III clinical trial, distribution / licencing agreements, and future development of AV0113 for other cancers.

Please see Douglas Lloyd Fell’s contact details below:
Phone: + 44 7770 445 268
Email: douglas.lloyd-fell@activartis.com

Please note: Any medical or scientific information published on this website is not intended as a substitute for informed medical advice from a physician and you should not take any action before consulting with a health care professional. For more information, please read my terms & conditions.

4 comments:

  1. My friend's dad just died of cancer.
    I am really hoping that your research will be successful and that you'll find a way to beat this disease. Thank you for what you do.

    ReplyDelete
    Replies
    1. Hi Jessica, Thank you for getting in touch. Sorry to hear your friend's dad died of cancer. It is these types of unfortunate stories which are the reason for starting my blog.
      People who are diagnosed with terminal cancer, aren't necessarily familiar with medicine or science, and as such may be missing out on potentially lifesaving new developments.
      With the hope that it will be useful to end-stage cancer patients (by giving them information on how new therapies work and perhaps more importantly where to gain access) I started publishing articles about new / interesting drug developments on my blog. Once again, thank you very much for reaching out.

      Delete
  2. Thank you for the information and this has led me further research about immunotherapy and found out that Malaysia's hospitals have adopted it. My father is currently going through chemotherapy and he suffered a lot. Thank you so much for sharing this information and this has help us to explore alternative treatment for our father. http://www.thestar.com.my/Lifestyle/Health/2011/02/27/New-approach-to-cancer-therapy.aspx/

    ReplyDelete
    Replies
    1. Hi Adeline, Thank you for your kind words. It's great to hear that cancer immunotherapy is gaining momentum in Malaysia. Thank you for sharing that information and for commenting on my blog.

      Delete