CAR-T Cells Surface-Engineered with Drug-Encapsulated Nanoparticles Can Ameliorate Intratumoral T-cell Hypofunction.

Abstract:

:One limiting factor of CAR T-cell therapy for treatment of solid cancers is the suppressive tumor microenvironment (TME), which inactivates the function of tumor-infiltrating lymphocytes (TIL) through the production of immunosuppressive molecules, such as adenosine. Adenosine inhibits the function of CD4+ and CD8+ T cells by binding to and activating the A2a adenosine receptor (A2aR) expressed on their surface. This suppression pathway can be blocked using the A2aR-specific small molecule antagonist SCH-58261 (SCH), but its applications have been limited owing to difficulties delivering this drug to immune cells within the TME. To overcome this limitation, we used CAR-engineered T cells as active chaperones to deliver SCH-loaded cross-linked, multilamellar liposomal vesicles (cMLV) to tumor-infiltrating T cells deep within the immune suppressive TME. Through in vitro and in vivo studies, we have demonstrated that this system can be used to effectively deliver SCH to the TME. This treatment may prevent or rescue the emergence of hypofunctional CAR-T cells within the TME. Cancer Immunol Res; 6(7); 812-24. ©2018 AACR.

journal_name

Cancer Immunol Res

authors

Siriwon N,Kim YJ,Siegler E,Chen X,Rohrs JA,Liu Y,Wang P

doi

10.1158/2326-6066.CIR-17-0502

subject

Has Abstract

pub_date

2018-07-01 00:00:00

pages

812-824

issue

7

eissn

2326-6066

issn

2326-6074

pii

2326-6066.CIR-17-0502

journal_volume

6

pub_type

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