Allogeneic lymphocyte-licensed DCs expand T cells withimproved antitumor activity and resistance to oxidative stress andimmunosuppressive factors

Jin, ChuanUppsala universitet,Institutionen för immunologi, genetik och patologi,Science for Life Laboratory, SciLifeLab (author)

De två sista författarna delar sistaförfattarskapet.
Adoptive T-cell therapy of cancer is a treatment strategy where T cells are isolated, activated, in some cases engineered, and expanded ex vivo before being reinfused to the patient. The most commonly used T-cell expansion methods are either anti-CD3/CD28 antibody beads or the “rapid expansion protocol” (REP), which utilizes OKT-3, interleukin (IL)-2, and irradiated allogeneic feeder cells. However, REP-expanded or bead-expanded T cells are sensitive to the harsh tumor microenvironment and often short-lived after reinfusion. Here, we demonstrate that when irradiated and preactivated allosensitized allogeneic lymphocytes (ASALs) are used as helper cells to license OKT3-armed allogeneic mature dendritic cells (DCs), together they expand target T cells of high quality. The ASAL/DC combination yields an enriched Th1-polarizing cytokine environment (interferon (IFN)-γ, IL-12, IL-2) and optimal costimulatory signals for T-cell stimulation. When genetically engineered antitumor T cells were expanded by this coculture system, they showed better survival and cytotoxic efficacy under oxidative stress and immunosuppressive environment, as well as superior proliferative response during tumor cell killing compared to the REP protocol. Our result suggests a robust ex vivo method to expand T cells with improved quality for adoptive cancer immunotherapy.

MEDICIN OCH HÄLSOVETENSKAP Medicinska och farmaceutiska grundvetenskaper Immunologi inom det medicinska området hsv//swe
MEDICAL AND HEALTH SCIENCES Basic Medicine Immunology in the medical area hsv//eng
rapid expansion protocol
adoptive T cell transfer
immunosuppression
oxidative stress
immunotherapy
T cell expansion protocol
allogeneic lymphocytes
dendritic cells
Immunologi
Immunology

Yu, DiUppsala universitet,Institutionen för immunologi, genetik och patologi,Science for Life Laboratory, SciLifeLab(Swepub:uu)diayu422 (author)
Hillerdal, VictoriaUppsala universitet,Science for Life Laboratory, SciLifeLab,Klinisk immunologi(Swepub:uu)vicra286 (author)
Wallgren, AnnaCarinUppsala universitet,Institutionen för immunologi, genetik och patologi,Science for Life Laboratory, SciLifeLab(Swepub:uu)annawall (author)
Karlsson-Parra, AlexUppsala universitet,Science for Life Laboratory, SciLifeLab,Klinisk immunologi(Swepub:uu)aka12694 (author)
Essand, MagnusUppsala universitet,Klinisk immunologi,Science for Life Laboratory, SciLifeLab(Swepub:uu)magnessa (author)
Uppsala universitetInstitutionen för immunologi, genetik och patologi (creator_code:org_t)

In:Molecular Therapy Methods & Clinical Development: Nature Publishing Group12329-0501

By the author/editor: Jin, Chuan; Yu, Di; Hillerdal, Victo ...; Wallgren, AnnaCa ...; Karlsson-Parra, ...; Essand, Magnus

About the subject

MEDICAL AND HEALTH SCIENCES: MEDICAL AND HEAL ...; and Basic Medicine; and Immunology in th ...

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