This work was presented at the American Society for Hematology conference very recently, and to my knowledge has not yet been fully published. Essentially, what the researchers did is remove T-cells from the patients with cancers, transduce them with a chimeric antigen receptor (CAR) that targets the CD19 antigen found on most leukemia/lymphoma cells. This allows the newly engineered cells to seek out and kill all cells with the CD19 antigen, so in essence the cancer. While this is very promising, there are a lot of potential pitfalls. One is that normal B-cells express CD19, and the authors report long-term B-cell depletion in subsets of patients. Another is the long term ramifications. It is unclear if the engineered cells will act in a normal fashion, and potentially not become malignant themselves. Last, one major limitation to this method is the rapid rate of cancer killing. Often overlooked in the research world is the RATE in which you kill the cancer cells. If this is done too quickly, you can send patients into acute toxicity by liver and kidney damage due to an overload of toxins. This new methodology not only kills cells very rapidly leading to this potential for toxicity, but there is an overwhelming amount of pro-inflammatory cytokine production produced by the engineered cells which exacerbates the toxicity even further. Overall, this is a great step forward, but more studies need to be performed to establish the long-term effects and to decrease potential adverse side effects. You can read the primary abstract here:

https://ash.confex.com/ash/2013/webprogram/Paper62867.html

~Adam

I don't know that why editor deleted this post yesterday? anyway, I wrote this post again, please write and go on your idea...

This work was presented at the American Society for Hematology conference very recently, and to my knowledge has not yet been fully published. Essentially, what the researchers did is remove T-cells from the patients with cancers, transduce them with a chimeric antigen receptor (CAR) that targets the CD19 antigen found on most leukemia/lymphoma cells. This allows the newly engineered cells to seek out and kill all cells with the CD19 antigen, so in essence the cancer. While this is very promising, there are a lot of potential pitfalls. One is that normal B-cells express CD19, and the authors report long-term B-cell depletion in subsets of patients. Another is the long term ramifications. It is unclear if the engineered cells will act in a normal fashion, and potentially not become malignant themselves. Last, one major limitation to this method is the rapid rate of cancer killing. Often overlooked in the research world is the RATE in which you kill the cancer cells. If this is done too quickly, you can send patients into acute toxicity by liver and kidney damage due to an overload of toxins. This new methodology not only kills cells very rapidly leading to this potential for toxicity, but there is an overwhelming amount of pro-inflammatory cytokine production produced by the engineered cells which exacerbates the toxicity even further. Overall, this is a great step forward, but more studies need to be performed to establish the long-term effects and to decrease potential adverse side effects. You can read the primary abstract here:

https://ash.confex.com/ash/2013/webprogram/Paper62867.html

~Adam

http://www.nature.com/nbt/journal/v31/n11/full/nbt.2725.html;

This paper was posted. But I don't know who it was. It is a very interesting one on this topic.

My comment and thought was: The problem with "hunting" cancer cells with T-cells from patient himself, is autoimmune reactivity. (it is also discussed in the linked nature review )

Here's the link to the Hematology conference where the engineered T cell work was presented. The researchers most responsible for presenting these developments seem to be: Grupp, June, Porter and Kalos. Very promising work.

Hematology Conference

http://www.hematology.org/News/2013/11771.aspx

Childrens Hospital of Philadelphia info:

http://www.chop.edu/news/chop-presents-t-cell-therapy-research-update.html

Problems arising with the use of chimeric TCRs in cancer therapy are well described in the review by Christian Hinrichs and Nicholas Restifo.

https://www.researchgate.net/publication/258061317_Reassessing_target_antigens_for_adoptive_T-cell_therapy

There is great risk to induce autoimmune side-effects in patient. The approach need further investigations aimed on identification of tumor antigens (really, autoantigens), targeting of which will result in minimal damage to vital functions. Second point is that technical solution is required to stop developing unwanted immune reactions if necessary.

Article Reassessing target antigens for adoptive T-cell therapy

Adoptive T cell therapy with transduced T cells has been going on for quite some time. The T cells can have first, second or third generation chimeric antigen receptors (CAR) based on the signaling domains within the cell. As mentioned in almost all the posts, the major problem is T cell mediated toxicity. One possibility to avoid these is to include a safety switch in the T cells. Thus the transduced T cells have both CAR and this inducible suicide gene. When this safety switch is turned on, by administering a special drug, the T cells commit suicide. The following paper in NEJM used this approach back in 2011.

Inducible Apoptosis as a Safety Switch for Adoptive Cell Therapy

Antonio Di Stasi et al.

PMID: 22047558

I watched seminar saying CTLA4, T cell receptor can be therapeutic agent for melanoma, others I know so far are PD1inhibitors. But, our research showed that NK cells can be useful therapeutic agents for cancer.

I watched seminar saying CTLA4, T cell receptor can be therapeutic agent for melanoma, others I know so far are PD1inhibitors. But, our research showed that NK cells can be useful therapeutic agents for cancer.