Lipophilic recombinant-protein insertion endows lymphocytes with enhanced targeting-infiltration ability in EGFR positive cancer.
Cell Immunol
; 365: 104376, 2021 07.
Article
in En
| MEDLINE
| ID: mdl-33984534
ABSTRACT
Adoptive T cell transfer is one of the most promising ways to combat solid tumors. However, the weak infiltration of T cells into tumor sites has restricted their antitumor efficacy. To overcome this obstacle, we used the lipophilic protein painting strategy to improve tumor targeting and penetrating capacity of lymphocytes for the first time. We synthesized the lipid anchor consisting of a bispecific recombinant protein iRGD-antiEGFR and DSPE-PEG derivates, then successfully inserted it into the membranes of T cells. This surface modification was non-invasive and could efficiently improve the infiltration ability of T cells into multicellular spheroids and tumor masses. The surface modified T cells also displayed superior antitumor activities in EGFR-positive tumor xenografts via systematic infusion. Moreover, the permeability and antitumor efficacy of these surface painted T cells could be remarkably enhanced when used in combination with local low-dose irradiation.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Stomach Neoplasms
/
Receptors, Antigen, T-Cell
/
T-Lymphocytes
/
Cell Membrane
/
Immunotherapy, Adoptive
/
Lymphocytes, Tumor-Infiltrating
/
Single-Domain Antibodies
Type of study:
Prognostic_studies
Limits:
Animals
/
Humans
/
Male
Language:
En
Journal:
Cell Immunol
Year:
2021
Document type:
Article
Affiliation country:
China