Treating hematological malignancies with cell therapy: where are we now?

ABSTRACT

Introduction: Adoptive cell therapy (ACT) is becoming an increasingly successful and widespread form of treatment for different types of cancer. Compared to chemotherapy or monoclonal antibodies, ACT is an active biological strategy, with infused immune cells featuring dynamic migration, expansion and long-term persistence properties. ACT in hematological malignancies offered the initial proof of principle of the feasibility for this innovative ‘live-drug’.

Areas covered: In this review, the authors summarize the clinical results achieved with two specific strategies in hematological malignancies: chimeric antigen receptor (CAR) and T cell receptor (transgenic TCR) redirected T cells. Moreover, they discuss the recent pre-clinical studies aimed at increasing the feasibility, safety and efficacy of ACT.

Expert opinion: ACT can promote cancer regression in patients with leukemia, lymphoma and multiple myeloma. Nevertheless, more precise targeting of tumor cells and containment of side effects are needed. Overcoming tumor-associated immunosuppressive mechanisms and preventing tumor escape are also emerging as critical barriers. Finally, simplification in the manufacturing procedures should promote wider application of these technologies outside academic centers. Although the enthusiasm for ACT-based therapies is high, comprehensive and systematic clinical studies are required to advance the field.

KEYWORDS:

• Adoptive cell therapy
• hematologic malignancies
• T cell receptor
• chimeric antigen receptor
• transgenic TCR
• CAR T cells

Article highlights

• Adoptive cell therapy (ACT) is based on the ex vivo activation and expansion of tumor reactive T cells to large numbers and their re-infusion to a cancer patient after lymphodepleting conditioning.

• T cells can be redirected towards cancer antigens through a genetic manipulation that allows the insertion of a tumor-specific chimeric antigen receptor (CAR) or a T cell receptor (TCR).

• ACT obtained remarkable results in the treatment of hematological malignancies especially with CAR-T cells targeting the CD19 glycoprotein.

• Both CAR and TCR-redirected T cells can mediate tumor elimination, although, improvements are still required to increase the efficacy, persistence, and availability of gene-modified T cells.

• Several efforts attempted to endow redirected-T cells with a safer profile. Research is still ongoing to reduce and potentially prevent toxic effects related to T cells activation, expansion, and target recognition in vivo.

• One of the most revolutionary characteristics of cancer cell immunotherapy is the potential to eradicate the disease with a ‘one-time’ treatment and the prospective to establish long-term protection.

This box summarizes key points contained in the article.

Acknowledgments

The authors would like to thank Kathryn M Petrosimone for editing the manuscript

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Additional information

Funding

The authors are supported by a National Institute of Health grant via the National Heart, Lung and Blood Institute [RO1-HL114564-03], a Tier 2-Stimular Award and the University Cancer Research Fund from the Lineberger Comprehensive Cancer Center of the University of North Carolina and the Leukemia and Lymphoma Society [grant no. SCOR 7001-14].