التفاصيل البيبلوغرافية
| العنوان: |
Comprehensive Approach for Identifying the T Cell Subset Origin of CD3 and CD28 Antibody-Activated Chimeric Antigen Receptor-Modified T Cells. |
| المؤلفون: |
Schmueck-Henneresse, Michael1,2,3,4 michael.schmueck-henneresse@charite.de, Omer, Bilal4,5,6,7, Shum, Thomas4,5,6,8, Haruko Tashiro4,5,6, Mamonkin, Maksim4,5,6, Lapteva, Natalia4,5,6, Sharma, Sandhya4,5,6,8, Rollins, Lisa4,5,6, Dotti, Gianpietro4,5,6, Reinke, Petra2,3, Volk, Hans-Dieter1,2, Rooneyx, Cliona M.4,5,6,9,10 |
| المصدر: |
Journal of Immunology. 7/1/2017, Vol. 199 Issue 1, p348-362. 15p. |
| مصطلحات موضوعية: |
*T cells, *CD3 antigen, *CD28 antigen, *CHIMERIC antigen receptors, *IMMUNOLOGIC diseases, *IMMUNOREGULATION, *PHYSIOLOGY |
| مستخلص: |
The outcome of therapy with chimeric Ag receptor (CAR)-modified T cells is strongly influenced by the subset origin of the infused T cells. However, because polyclonally activated T cells acquire a largely CD45RO+CCR7- effector memory phenotype after expansion, regardless of subset origin, it is impossible to know which subsets contribute to the final T cell product. To determine the contribution of naive T cell, memory stem T cell, central memory T cell, effector memory T cell, and terminally differentiated effector T cell populations to the CD3 and CD28-activated CAR-modified T cells that we use for therapy, we followed the fate and function of individually sorted CAR-modified T cell subsets after activation with CD3 and CD28 Abs (CD3/28), transduction and culture alone, or after reconstitution into the relevant subset-depleted population. We show that all subsets are sensitive to CAR transduction, and each developed a distinct T cell functional profile during culture. Naive-derived T cells showed the greatest rate of proliferation but had more limited effector functions and reduced killing compared with memory-derived populations. When cultured in the presence of memory T cells, naive-derived T cells show increased differentiation, reduced effector cytokine production, and a reduced reproliferative response to CAR stimulation. CD3/28-activated T cells expanded in IL-7 and IL-15 produced greater expansion of memory stem T cells and central memory T cell-derived T cells compared with IL-2. Our strategy provides a powerful tool to elucidate the characteristics of CAR-modified T cells, regardless of the protocol used for expansion, reveals the functional properties of each expanded T cell subset, and paves the way for a more detailed evaluation of the effects of manufacturing changes on the subset contribution to in vitro-expanded T cells. [ABSTRACT FROM AUTHOR] |
| قاعدة البيانات: |
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