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Strategies to Enhance Migration and Persistence of Chimeric Antigen Receptor (CAR)-T Cells into Tumors

  • Yuhui Chen
  • Gianpietro Dotti
  • Barbara SavoldoEmail author
Chapter
Part of the Resistance to Targeted Anti-Cancer Therapeutics book series (RTACT, volume 9)

Abstract

Since the past few decades, immunotherapy based on the adoptive transfer of tumor-specific T-cells is providing a promising form of cancer treatment. This result has been obtained through the improvement of the methodologies used to expand ex vivo antigen-specific T cells, and through technology advancements in T-cell engineering aimed at transferring into these cells chimeric antigen receptors (CAR) or αβTCRs chains. High enthusiasm is especially directed to the CAR technology, as this confers MHC-independent antigen-specificity to T cells, thus allowing broad clinical applications. The greatest advances have been achieved in lymphoid malignancies, while the clinical benefits of CAR-T cells to solid tumors still remain uncertain. In this review we will explore two of the problems that are currently perceived as limiting the success of the clinical translation of CAR-T cells in solid tumors: namely, the recruitment and survival of tumor-specific T cells in the microenvironment.

Keywords

Chimeric antigen receptor Immunotherapy Chemokines Migration and Infiltration Improving Persistence Overcoming immune-evasion 

Abbreviations

Bcl-2

B-cell lymphoma 2

Bcl-xL

B-cell lymphoma-extra large

CAR

Chimeric antigen receptor

CD

Cluster of Differentiation

CTLA4

Cytotoxic T-lymphocyte-associated protein 4

DPP4

Dipeptidyl peptidase 4

ECM

Extra cellular matrix

ERK

Extracellular signal-regulated kinases

GD2

Ganglioside Diasialo 2

GM-CSF

Granulocyte-macrophage colony-stimulating factor

Gro-α

Growth-regulated oncogene-α

HVEM

Herpes Virus Entry Mediator

IDO

Indoleamine 2, 3-dioxygenase

IFN

Interferon

IL

Interleukin

LAG3

Lymphocyte-activation gene 3

M2

Macrophages type 2

MDC

Macrophage-derived chemokine

MHC

major histocompatibility complex

MDSC

Myeloid derived suppressor cells

NF-kB

Nuclear factor-kB

NKGD2

Natural Killer Group 2D

PD1

Programmed cell death protein 1

PD-L1/PD-L2

Programmed death-ligand 1/2

PGs

Proteoglycans

RANTES

Regulated on Activation, Normal T Cell Expressed and Secreted

ROS

Reactive oxygen species

siRNA

Small interfering RNA

TARC

Thymus and activation-regulated chemokine

TCR

T cell receptor

Tregs

Regulatory T cells

Notes

Acknowledgements

This work was supported in part by a SCOR grant from the Leukemia and Lymphoma Society, RO1 1145564 from NHLBI, RO1CA193130 from NCI and Tier 2: Stimulus Award, Lineberger Comprehensive Cancer Center, University of North Carolina. The authors

Disclosure conflict-of-interest disclosure: No disclosure.

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Copyright information

© Springer International Publishing Switzerland 2016

Authors and Affiliations

  • Yuhui Chen
    • 1
  • Gianpietro Dotti
    • 1
    • 2
  • Barbara Savoldo
    • 1
    • 3
    Email author
  1. 1.Lineberger Comprehensive Cancer CenterUniversity of North CarolinaChapel HillUSA
  2. 2.Department of Microbiology and ImmunologyUniversity of North CarolinaChapel HillUSA
  3. 3.Department of PediatricsUniversity of North CarolinaChapel HillUSA

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