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Expert Opin Biol Ther. 2015 Mar;15(3):403-16. doi: 10.1517/14712598.2015.1014792. Epub 2015 Feb 9.

Using gene therapy to manipulate the immune system in the fight against B-cell leukemias.

Author information

1
University of Chicago School of Medicine , Chicago, IL , USA.

Abstract

INTRODUCTION:

Over 20 years ago, chimeric antigen receptors (CARs) were created to endow T cells with new antigen-specificity and create a therapy that could eradicate cancer and provide life-long protection against recurrence. Steady progress has led to significant improvements with CAR design and CAR T-cell production, allowing evaluation of CAR T cells in patients. The initial trials have targeted CD19, which is expressed on normal and malignant B cells.

AREAS COVERED:

We review data from trials for patients with chronic lymphocytic leukemia (CLL) and B-cell acute lymphoblastic leukemia (B-ALL). In addition, we discuss the on-target toxicities, B-cell aplasia and cytokine release syndrome (CRS), which is uniquely associated with T-cell immunotherapies.

EXPERT OPINION:

We compare the results when targeting the same antigen in CLL or B-ALL and speculate on reasons for outcome differences and future directions to enhance outcomes. Furthermore, the dramatic results targeting B-ALL require further analysis in Phase II trials, and we discuss important components of these future trials. We also suggest a management scheme for CRS. The next several years will be critical and may lead to the first clinical indication of a gene-engineered cell therapy for cancer.

KEYWORDS:

B-cell acute lymphoblastic leukemia; adoptive T-cell therapy; chimeric antigen receptors; chronic lymphocytic leukemia; gene therapy; immunotherapy

PMID:
25666545
PMCID:
PMC4586131
DOI:
10.1517/14712598.2015.1014792
[Indexed for MEDLINE]
Free PMC Article

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