Format

Send to

Choose Destination
Oncoimmunology. 2018 Sep 6;7(12):e1500674. doi: 10.1080/2162402X.2018.1500674. eCollection 2018.

Actin stabilizer TAGLN2 potentiates adoptive T cell therapy by boosting the inside-out costimulation via lymphocyte function-associated antigen-1.

Jeon BN1,2, Kim HR1,2, Chung YS1,2, Na BR1,2, Park H1,2, Hong C1,2, Fatima Y1,2, Oh H1,2, Kim CH1,2, Jun CD1,2.

Author information

1
School of Life Sciences, GIST, Gwangju, Korea.
2
Immune Synapse and Cell Therapy Research Center, GIST, Gwangju, Korea.

Abstract

Correct temporal and spatial control of actin dynamics is essential for the cytotoxic T cell effector function against tumor cells. However, little is known whether actin engineering in tumor-targeted T cells can enhance their antitumor responses, thereby potentiating the adoptive T cell therapy. Here, we report that TAGLN2, a 22-KDa actin-stabilizing protein which is physically associated with lymphocyte function-associated antigen-1 (LFA-1), potentiates the OTI TCR CD8+ T cells to kill the intercellular adhesion molecule-1 (ICAM-1)-positive/OVA-presenting E0771 cells, but not ICAM-1-negative OVA-B16F10 cells, suggesting an 'inside-out' activation of LFA-1, which causes more efficient immunological synapse formation between T cells and tumor cells. Notably, recombinant TAGLN2 fused with the protein transduction domain (TG2P) overcame the disadvantages of viral gene delivery, leading to a significant reduction in tumor growth in mice. TG2P also potentiated the CD19-targeted, chimeric antigen receptor (CAR)-modified T cells to kill Raji B-lymphoma cells. Our findings indicate that activating the TAGLN2-actin-LFA-1 axis is an effective strategy to potentiate the adoptive T-cell immunotherapy.

KEYWORDS:

ICAM-1; LFA-1; PTD; TAGLN2; adoptive T cell therapies; cancer immunotherapy

Supplemental Content

Full text links

Icon for Taylor & Francis Icon for PubMed Central
Loading ...
Support Center