Posted by on April 22, 2018 12:51 pm
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Source: Fate the company launched the iPSC combination of CRISPR generation of”pure”Universal CAR-T cells

2018 4 November 20/medical Mai guest eMedClub/–FT819 is aoff the shelf(spot), TCR-less(completely eliminate TCR)the CD19 CAR T cell product, with conventional CAR-T cell therapy compared to its for cancer patients, may be more easily obtained.

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Recently, the held in Chicago in 2018 AACR annual meeting, theFate Therapeutics, the company’s cancer immunotherapy, Vice President—Bob Valamehr, Dr announced that a groundbreaking CAR-T therapies before clinical studies resultshighlight the specificity, functionality, and effectiveness.

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It is well known, at present, a chimeric antigen receptor(CAR)T cell therapy has been in some cancer patients showed a very significant therapeutic effect,but this highly personalized treatment, the production preparation time is very long, and enough cells can only be used for the variable parameters(weight of the patient mixed)single-dose therapy.

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In addition, Bob Valamehr Dr. also added:most in the study of CAR – T cell therapy is only directed against a single tumor antigen, and this will also limit the therapeutic effect.

Based on the above mentioned challenges, theFate Therapeutics, the company developed an off the shelf(stock), double the target point of the CAR-T cell product—FT819 it.different from the autologous CAR-T cell therapy,FT819 from healthy donor subjects the cells to start, rather than the patient’s own cells, and then create a primary cell line, and the use of primary cell lines produce large amountsnot subject to the patient limits the“Universal”CAR19 T cells.Valamehr, explains:“these named FT819category headerCAR19 T cells can be Packed, stored, and ultimately used a large number of cancer patients.”

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Specifically, for the production of manufacturing FT819 primary cell lines are induced pluripotent stem cells(iPSC)lines. With autologous(from the use of the patient’s own cells)and allogeneic(using from the donor of the cells)method compared to the use of the primary iPSC line production of CAR-T cells have a distinct advantage. Including:the primary iPSC lines have unlimited self-renewal capacity, and can be stored and renewable use.Valamehr and colleagues used their previously developed patented platform to create a master iPSC lines.

But at the same time, the use of donor T cells��The manufacture of CAR-T cells it must be noted that donor T cells will attack the patient’s tissues and organs, resulting in potentially severe and fatal immune system reaction called graft-versus-host disease(GvHD).< strong>in order to avoid GvHD, Valamehr explained, closing or removal of the TCR is essential.

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Will, Valamehr noted that the researchers try to design billions of large-scale donor T cells, through the Elimination of TCR challenge. Ultimately, the researchers through the CAR Guide to a single pluripotent cells of the T cell receptor Alpha constant(TRAC)gene holder, to ensure that completely eliminate the TCR.< strong>FT819 completely eliminate the TCR, a pure CAR expression,as we passed several clinical tests learned thateven if there is very little expression of the TCR cells also cause GVHD, and therefore, this pure CAR expression product is now secure and efficient.

As FT819 project collaborators,CAR-T large cow,Memorial Sloan Kettering Cancer Center of Michel Sadelain, Dr. has been previously proved,on the TRAC site under the control of the CAR of the expression is consistent with enhanced T-cell effectiveness, and in acute lymphoblastic leukemia mouse model, greatly superior to the conventional generation of CAR-T cells.

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Further, in addition to the targeting CD19-positive tumor cells in the CAR,FT819 also has aims to expand the effectiveness of the second target to the receptor, the CD16Fc receptor can be combined with antibody-coated tumor cells. This makes FT819 can be combined with other proven cancer treatments(such as targeting CD20-positive tumor cells, monoclonal antibody)administered in combination to potentially overcome tumor antigen escape.

In in vitro studies,FT819 through the production of cytokines(IFN-γ, TNF-α, and IL2)and cell death in medium(CD107a/b, perforin, and granzyme B)stimulation of CD19-positive tumor cells showed efficient cytotoxic T cell response.also found FT819 having targeting specificity, only to attack CD19-positive tumor cells, while ignoring the CD19 negative tumor cells. By CD16Fc receptor expression,when targeting CD20 therapeutic antibody combination, FT819 shown to cause antibody-dependent cell-mediated cytotoxicity.

Valamehr, said:“by FT819 development, we believe itfor reducing CAR-T cell production costs, improve product quality, create more efficient supply of products has major significance,this will enable more cancer patients to get effective treatment.”

Of course, FT819 used in the study of the model system is not able to predict the clinical safety and effectiveness, and therefore, thecompany next to conduct human clinical trials will be fully evaluated, this ready-made(off the shelf), the iPSC-derived CAR T cells product safety and effectiveness.

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In summary, Fate Therapeutics company in the research of FT819, is a clone project of the main pluripotent cell lines(MPCL)to produce a new generation of CAR-CD8α+ T cells. Wherein the main pluripotent cell lines(MPCL)is composed of induced pluripotent stem cells(iPSC)generated using CRISPR/Cas9 technology to the CAR insert the T cell receptor Alpha constant(TRAC)gene holder, at the same time completely eliminate the T cell receptor(TCR)expression. Makes this called FT819 of CAR-T cell therapy product, not limited to music, and be able to achieve large-scale production(off the shelf management mode).< strong>

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Original title: AACR to the forefront:the dark horse Fate the company launched the iPSC combination of CRISPR generation of”pure”Universal CAR-T cells, or can be breakthrough personalized limitations, to achieve large-scale production

Reference source:

https://medicalxpress.com/news/2018-04-off-the-shelf-dual-targeted-car-t-cell-product.html

http://www.targetedonc.com/conference/aacr-2018/findings-with-ft819-demonstrate-promising-accessible-approach-to-car-tcell-therapy

http://ir.fatetherapeutics.com/

*statement: this article by the settled Sina pharmaceutical news authored, the views are those of the authors themselves, does not mean Sina pharmaceutical News Stand.

Published at Sun, 22 Apr 2018 12:51:22 +0000

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