Curator: Meg Baker, PhD, Reg Patent Agent
http://www.uphs.upenn.edu/news/News_Releases/2012/08/novartis/
Novartis provides funding for research of modified T cell treatments. Successful application of the technique was demonstrated in a clinical study led by Dr. Carl June, a pathologist at the University of Pennsylvania, for CLL (chronic lympocytic leukemia), one of the most common types of leukemia. The initial study report was in August 2011 http://www.uphs.upenn.edu/news/News_Releases/2011/08/t-cells/
The concept of doctoring T-cells genetically was first developed in the 1980s by Dr. Zelig Eshhar at the Weizmann Institute of Science in Rehovot, Israel. It involves adding gene sequences from different sources to enable the T-cells to produce what researchers call chimeric antigen receptors, or CARs — protein complexes that transform the cells into, in Dr. June’s words, “serial killers.” See http://www.nytimes.com/2011/09/13/health/13gene.html?pagewanted=all
Dr. June describes the new therapy as “ultrapersonalized” because the treatments involve extracting a patient’s immune cells and using deactivated HIV-1 to deliver genes into the cells, and later infusing in the re-educated cells back into patient’s system. The treatment is characterized as “training the immune system” to attack cancer. Thus, it is hoped that the technology can be applied more broadly to cancer therapy.
Read more: Novartis backs UPenn’s pioneering cancer immunotherapies – FierceBiotech http://www.fiercebiotech.com/story/novartis-backs-upenns-pioneering-cancer-immunotherapies/2012-08-06#ixzz25tGYGQ9N
Subscribe: http://www.fiercebiotech.com/signup?sourceform=Viral-Tynt-FierceBiotech-FierceBiotech
NYT article: http://www.nytimes.com/2012/08/06/business/novartis-and-penn-unite-on-anticancer-approach.html
[…] Comments « Center for Advanced Cellular Therapies at U Penn gets $20MM funding from Novartis […]
[…] Visit link: Center for Advanced Cellular Therapies at U Penn gets $20MM … […]
I don’t understand the generalization of the model developed at Weizzman Institute to the retraining of T cells infected with inactivated HIV1.
Google dr. Zelig Eshhar at Weitzman Institute
http://www.weizmann.ac.il/immunology/sci/EshharPage.html
In order for the T-cells to cause immune activation in response to binding specific targets, there must be both a target binding event and receptor ligation in the form of e.g. and antibody FcR domain or T-cell receptor embedded in the membrane. CARs combine antigen-specificity with T cell activation in a single fusion molecule. Most CARs are comprised of an antigen-binding domain, an extracellular spacer/hinge region, a trans-membrane domain and an intracellular signaling domain resulting in T cell activation after antigen binding.
Thanks a lot for this help from both you and Aviva.
This area of research is really at the leading edge. I’ll follow this up for my own curiosity. It is light years from my work with embryology and with trophoblasts in 1967. I look at the trajectory of knowledge growth and it is like a shooting star.
In addition, I have to check up on the immune-deficient mice. I learned from the University of California scientific files a few weeks ago that prior to his death, NO Kaplan and Gordon Sato had developed such a strain of athymic mice that they made available for any scientists to investigate cancer. This was really a divergence from what he had spent years engaged in. His most famous postdoc was the Founder of Celeris, who completed the DNA just before the NIH.
This work in Israel takes us to the very foundation of modification of thymic cell derived immunity.
Dr. Larry,
Do you me member our talk about my friend who had a tumor in her thymus gland, you said that it is very rare.
I suggest that, since you mentioned yourvown curiosity, than, how about if you will target three papers on the work of Dr. Zelig Eshhar and built one post for our research category Human Immune System
OK. I’ll learn a lot. Just like coagulation, this is a subject that professionals with good knowledge have difficulty. This will take some hard work, but I’ll start right away. It was my work with stess hypermetabolism that drew me into learning more about cellul mediated immunity, with emphasis on the Bursal system. When I started research I worked with antibody mediated and was in protein separation, then using starch gel developed by David Poulik, from Canada.
It’s vastly more complicated than we were taught. Then it was Medawar and Robert Good.
As I understand it, an alternative to modifying T-cells with CAR, is to create a “tri-specific” reagent to 1) bind target cell-specific antiggen 2) bind T-cells (e.g. bind CD3) and 3) activate effector functions by ligation of the CD16 (FcGammaIII receptor). See for example, US Patent No. 6551592. This is a very complex approach wherein the logistics and interplay of pharmacokinetics and pharmacodynamics as well as local spatial orientation of all three receptors, has to be optimized.
Yes, the T-cell subpopulations and receptor interplay are very complex. Tregs (formerly suppressor T or Tsup) have been brought to the fore. See for example http://www.jimmunol.org/content/186/12/6905.full . So other approaches to cancer therapy are aimed to releive the stimulation of the suppressing signals.
I remember being at the Cancer Biology Research Lab at Stanford when Steve Rosenberg announced success of his lymphocyte plus IL2 therapy in 2 patients, and my boss thought the jib was up. That was 1987.
Dr. Baker,
Thank you for your comment, You are edifying us all. Dr. Larry will look into developing one post on the work of Dr. Eshhar at Weitzman for our category Human Immune System.
Great discussion and receptivity.
Thanks again.
You’re welcome.