Title:CAR T-cell Therapy: A New Era in Cancer Immunotherapy
Volume: 19
Issue: 1
Author(s): Androulla N. Miliotou and Lefkothea C. Papadopoulou*
Affiliation:
- Laboratory of Pharmacology, School of Pharmacy, Aristotle University of Thessaloniki, GR-54124 Thessaloniki, Macedonia,Greece
Keywords:
Cancer, immunotherapy, T-cell therapy, chimeric antigen receptor (CAR), genetic engineering, safety.
Abstract: Background: Cancer is one of the leading causes of death worldwide. Over the years, a
number of conventional cytotoxic approaches for neoplastic diseases has been developed. However,
due to their limited effectiveness in accordance with the heterogeneity of cancer cells, there is a constant
search for therapeutic approaches with improved outcome, such as immunotherapy that utilizes
and enhances the normal capacity of the patient’s immune system.
Methods: Chimeric Antigen Receptor (CAR) T-cell therapy involves genetic modification of patient’s
autologous T-cells to express a CAR specific for a tumor antigen, following by ex vivo cell expansion
and re-infusion back to the patient. CARs are fusion proteins of a selected single-chain fragment variable
from a specific monoclonal antibody and one or more T-cell receptor intracellular signaling domains.
This T-cell genetic modification may occur either via viral-based gene transfer methods or nonviral
methods, such as DNA-based transposons, CRISPR/Cas9 technology or direct transfer of in vitro
transcribed-mRNA by electroporation.
Results: Clinical trials have shown very promising results in end-stage patients with a full recovery of
up to 92% in Acute Lymphocytic Leukemia. Despite such results in hematological cancers, the effective
translation of CAR T-cell therapy to solid tumors and the corresponding clinical experience is limited
due to therapeutic barriers, like CAR T-cell expansion, persistence, trafficking, and fate within
tumors.
Conclusion: In this review, the basic design of CARs, the main genetic modification strategies, the
safety matters as well as the initial clinical experience with CAR T-cells are described.
