Immuno-oncology the biggest breakthrough

[shazie]

Some have been bold enough to call it a cure for cancer.

news.nationalpost.com/2014/...

[Cllcanada Top Poster CURE Hero]

CLL has benefited greatly for over 15 years from immunotherapy.... primarily with monoclonal antibodies, like Rituximab, ofatumumab, Gazyva (obinutuzimab), Campath, Zevalin, Bexxar, Lumiliximab and so forth...

New on the horizon are CLL vaccines, CXCR4 antagonists, and adoptive cellular immunotherapies such as chimeric antigen receptor–modified T cells, CD40 ligand gene therapy, ROR1 monoclonals like cirmtuzumab etc.

Certainly a very exciting field... no cure yet... but perhaps one day...

[AussieNeil Partner Administrator]

You can look on this as a continuation of what doctors have been doing for century or more; helping the body to heal itself. Only now, we are working at the selectively keyed molecular level, rather than using splints, bandages, knives and broadly acting drugs. What I find amazing is that immunotherapy works with CLL - which can be aptly called a cancer of the immune system.

The article mentions the promise offered by enhancing natural T-cells and specifically mentions the efforts of Novartis in this field. It is worth remembering that this work got its start when Dr Carl June of the University of Pennsylvania showed success with CLL and ALL patients:

uphs.upenn.edu/news/news_re...

That ground breaking research resulted in Novartis' alliance with the University of Pennsylvania and the FDA breaththrough approval for CAR-T cell CD19 therapy:

datamonitorhealthcare.com/c...

We really will have a huge breakthrough when we can specifically target just the cancerous CLL cells and leave the normal B-Lymphocytes untouched.

Neil

[gemit2000 in reply to AussieNeil]

In 2012 Chaya Venkat wrote about UPenn's T-cell immunotherapy studies and the breakthrough possibilities of targeting ROR1 instead to leave the healthy B-Cells untouched.

updates.clltopics.org/4544-...

An excerpt:

Any number of research groups are looking to see how to tweak the U.Penn CARs approach so as to keep the good parts going but fix the problem areas. Using a different target for the T-cells – something other than CD19 – so that they kill only the cancerous B-cells and spare the healthy B-cells is very much desired. A number of options are being considered and I have no doubt that we will build on the success of the ground breaking success of the U. Penn team.

M. D. Anderson and others are looking at something called ROR1. What makes this marker hugely attractive is that it is expressed by CLL cells – but not healthy B-cells. IF everything goes according to plan, the hope is that ROR1 targeted T-cells will survive long enough in the body to kill each and every CLL cell in the body, but not damage the healthy B-cells. In other words, the patient is cured of CLL and yet healthy B-cell populations can recover and go on to produce plasma cells, immunoglobulins etc. By using ROR1 as the target of the killing power of the engineered T-cells, we can hope for avoiding the IVIG dependence baked into the cake of the U. Penn approach.

************

MD Anderson did start this clinical trial in July, tho' not yet recruiting. Of course, though B-cells would be untouched, with this variation there are other healthy cells at risk, creating its own issues. Alas the story of medical research - there are always downsides; the goal of each successive advance hopes only to improve the healing effects and decrease the negative effects of current therapies.

Gene M.

[Graham2222]

Fascinating, and very encouraging isn't it. Would Ibrutinib as a sole agent be classed as immunotherapy, in that it disrupts the communication system of the CLL cells and enables the body's natural defences to overcome them?

[Cllcanada Top Poster CURE Hero in reply to Graham2222]

No Imbruvica (ibrutinib) and Zydelig (idelalisib) among others are a new class of drugs called B cell receptor BCR, inhibitors...

Broadly they are:

Antineoplastic agent, Biologic Response Modifier, Signal Transduction Inhibitors.

[Graham2222]

Thanks for explaining.

[Cllcanada Top Poster CURE Hero in reply to Graham2222]

There is another inhibitor, ABT-199, that binds to B-cell lymphoma-2 (BCL-2) protein and restores, the 'cell death' signal [appoptosis] that is lost on malignant B cells.

I guess very broadly it would be immunotherapy, depends on how thin you want to slice the definition...

More

biooncology.com/pipeline-mo...

[Graham2222]

It probably helps in explaining to friends and family, who know of immunology-therapy from press reports in the UK, but go blank when I talk about B Cell Receptors!

[Cllcanada Top Poster CURE Hero in reply to Graham2222]

Yes, I tell people it isn't chemopherapy, but it uses the body's immune system to fight the cancer in various ways... and just leave it at that...

[alexmcg48 in reply to Cllcanada]

Forgive my ignorance, but isn't CLL basically a problem with the bodies natural immune system? If so, how would this treatment help with this condition?

[Cllcanada Top Poster CURE Hero in reply to alexmcg48]

Here is an example of how the man made antibody Rituxan works...

rituxan.com/hem/hcp/mechani...

Basically, they use other parts of the immune system to attack the B cells...

Video

youtube.com/watch?app=deskt...

The science

ncbi.nlm.nih.gov/pmc/articl...

[alexmcg48]

OK thanks, sounds very promising.

[SeymourB]

This article on CART immunotherapy has some nice animation to explain how it works. The article mentions CLL, but focuses on cancer in general:

cen.acs.org/articles/92/i40...