TRUCKs: the fourth generation of CARs.

Abstract

INTRODUCTION:

Adoptive cell therapy of malignant diseases takes advantage of the cellular immune system to recognize and destroy cancer cells. This is impressively demonstrated by redirecting T cells with a chimeric antigen receptor (CAR) towards CD19, inducing complete and lasting remission of leukemia in more than two-thirds of patients in early phase trials.

AREAS COVERED:

We outline how the CAR strategy is highly specific in redirecting T cells towards pre-defined target cells, however, reaches its limits when targeting solid tumors with a tremendous phenotypic heterogeneity. After initial tumor reduction by CAR T cells, antigen-negative cancer cells not recognized by CAR may give rise to tumor relapse. The situation may be overcome by CAR-mediated activation of T cells in the tumor, releasing inducible IL-12 which augments T-cell activation and attracts and activates innate immune cells to eliminate antigen-negative cancer cells in the targeted lesion.

EXPERT OPINION:

CAR T cells with a transgenic 'payload', so-called TRUCK T cells or the 'fourth-generation' CAR T cells, are worthwhile to explore to shape the tumor environment by the inducible release of transgenic immune modifiers. Such TRUCK T cells are moreover envisioned to be applied in fields beyond cancer therapy including the therapy of virus infections, auto-immune diseases or metabolic disorders.

• Authors: Markus Chmielewski, Hinrich Abken
• Journal: Expert opinion on biological therapy (Expert Opin Biol Ther) Vol. 15 Issue 8 Pg. 1145-54 ( 2015) ISSN: 1744-7682 [Electronic] England
• PMID: 25985798 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Review)

Chemical References

• Receptors, Antigen, T-Cell
• Interleukin-12

Topics

• Animals
• Humans
• Immunotherapy, Adoptive (methods)
• Interleukin-12 (immunology)
• Leukemia (immunology)
• Lymphocyte Activation (immunology)
• Receptors, Antigen, T-Cell (immunology)
• T-Lymphocytes (immunology)