[Beacon Staff]

Pfizer bets on Cellectis (and CAR T-cell therapy)

by Beacon Staff on Wed Jun 18, 2014 1:28 pm

The U.S. pharmaceutical company Pfizer has struck a deal with the French biotech firm Cellectis that gives Pfizer rights to a number of the products Cellectis is developing.

What is interesting about this development is that it demonstrates the growing interest in the so-called CAR-T approach to treating cancer. As Reuters explains in its report about the deal,

"Cellectis is developing Chimeric Antigen Receptor T-cell, or CAR-T, immunotherapies using engineered cells from a single donor for use in multiple patients.

This so-called allogeneic approach is in contrast to other autologous technologies that rely on engineering a patient's own T-cells and the aim is to make it possible to treat cancer using a standardised, off-the-shelf therapeutic product."

Reuters goes on to note that the Swiss pharmaceutical company Novartis "currently leads the field in CAR-T drug development, with autologous products in clinical trials for leukaemia, lymphoma, mesothelioma and pancreatic cancer."

As mentioned on the Cellectis website here, two of the products that it is developing -- but which are in the very early stages of development -- are aimed at multiple myeloma.

The two potential myeloma therapies go by the code names UCART-BCMA and UCART38. The two drugs also are mentioned in this slide deck from Cellectis which describes the company's CAR-T technology in more detail.

The Forbes article on the development has some additional background information about CAR-T that is very useful:

The CART field has become one of the hottest in drug development because the cells, though cumbersome and currently made individually for every patient, have shown amazing results in a small number of patients, making blood cancers seem to disappear and then stay vanished. ...

Cellectis’ cells are way behind all [its] competitors ... But the Cellectis approach is different because instead of arduously re-engineering a patients’ own white blood cells, it would aim to create an off-the-shelf product that could be given to many or any patient, simplifying production and distribution of the product."

The Bloomberg article on the development adds,

"Juno Therapeutics Inc., founded last year, is also testing drug candidates with a similar approach. The U.S. biotechnology company counts Amazon.com Inc. CEO Jeff Bezos among its investors ... The CAR-T technology developed by Cellectis hasn’t been tested in people yet, [analyst] Guerin said, so it’s difficult to assess whether the project will be a success."

In a Forbes article earlier this year, the CAR-T approach to cancer treatment is described this way:

"Scientists call [this new approach to treating cancer] chimeric antigen receptor T-cells, or CARTs. T-cells are the immune system’s most vicious hunters. They use their receptors to feel around in the body for cells with particular proteins on their surface and destroy them, targeting infected cells and cancer. With CARTs scientists add a man-made receptor–the chimeric antigen receptor–assembled from mouse antibodies and receptor fragments. A gene code for the man-made receptor is inserted into the T-cell’s DNA with a virus, usually a modified HIV. If the receptor sees cancer, not only does it kill it, it starts dividing, creating a cancer-killing army inside the body."

A study at the University of Pennsylvania that was publicized several years ago was the first that showed the real-life potential of the technology. It was so new at the time it wasn't even typically described as "CAR-T". The Beacon's article about the research can be found here,

https://myelomabeacon.org/news/2011/08/12/gene-therapy-advance-in-leukemia-suggests-new-treatment-options-for-multiple-myeloma/

and this follow-up article a year later discussed further developments:

https://myelomabeacon.org/news/2012/08/31/gene-therapy-to-treat-leukemia-and-multiple-myeloma-update/

The New York Times also has some useful (extended) articles on the subject:

http://www.nytimes.com/2011/09/13/health/13gene.html?pagewanted=all
http://www.nytimes.com/2012/12/10/health/a-breakthrough-against-leukemia-using-altered-t-cells.html?pagewanted=all

There also have been some discussions here in the forum about the CAR-T technology. For example,

https://myelomabeacon.org/forum/immunotherapy-car-t-cells-t3119.html

and one of the most popular ASH 2013 abstracts here at The Beacon was related to the technology:

https://myelomabeacon.org/resources/mtgs/ash2013/abs/14/

[Nancy Shamanna]

Re: Pfizer bets on Cellectis (and CAR T-cell therapy)

by Nancy Shamanna on Thu Jun 19, 2014 8:25 am

Thanks for this interesting information! Interesting that the CAR-T approach is termed 'allogenic' also. I suppose this means that the modified T-cells, that would attack myeloma cells specifically due to having the receptors to be targeted already genetically designed into them, come from outside the patient? Or is this an individual therapy where the patients own T cells are modified on an individual basis?

I think this is somewhat similar to the measles vaccine experimental therapy, where the measles vaccine was genetically altered and was shown to attack the multiple myeloma cells, but I could be off base here.

[Beacon Staff]

Re: Pfizer bets on Cellectis (and CAR T-cell therapy)

by Beacon Staff on Thu Jun 19, 2014 10:32 am

Thanks for your comment, Nancy.

Based on our reading of the various news reports, the Cellectis approach to CAR-T is unique precisely because it is allogeneic. That is, they are modifying stem cells provided by a donor and then using them in many other patients.

Thus far, the people who have been working on CAR-T methods have been focused on autologous approaches, where a patient's own stem cells are modified and then re-infused back into the patient.