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For the ADP-A2M4 SPEAR T-cell product co-expressing IL-7,

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jondoeuk   Sunday, 11/22/20 03:36:54 PM
Re: jondoeuk post# 112
Post # of 133 
For the ADP-A2M4 SPEAR T-cell product co-expressing IL-7, IL-15, dnTGF-B, and/or PDE7, previously, it has been shown that IL-15 alone could produce a small population of (stem central) memory cells, but combination with IL-7 should increase these numbers [1,2]. Thus, those two phenotypes have the potential to provide superior clinical outcomes [3,4].

A dnTGF-B receptor would help to improve the cytotoxic function of CD8+ T-cells [5,6], and reduce Treg conversion in CD4+ [7] caused by the cytokine [8].

As for PDE7, overexpression would confer resistance to the inhibitory effects of prostaglandin E2 (antigen-specific TCR downregulation) [9].

Refs:
1 https://ashpublications.org/blood/article/121/4/573/31229/IL-7-and-IL-15-instruct-the-generation-of-human
2 https://ashpublications.org/blood/article/101/11/4260/16861/Proliferation-and-differentiation-potential-of
3 https://www.pnas.org/content/102/27/9571.long
4 https://www.nature.com/articles/nm.2446
5 https://www.cell.com/cancer-cell/fulltext/S1535-6108(05)00331-4
6 https://www.cell.com/cancer-cell/fulltext/S1535-6108(05)00339-9
7 https://rupress.org/jem/article/194/5/629/20026/Cell-Contact-Dependent-Immunosuppression-by-Cd4
8 https://www.nature.com/articles/nri3902
9 https://www.cell.com/trends/immunology/fulltext/S1471-4906(01)02154-8

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