Development of CD30 CAR-T cells in refractory or relapsed Hodgkin’s lymphoma

ABSTRACT

Introduction

After therapy, approximately 15% of individuals with Hodgkin’s lymphoma (HL) develop relapsed or drug-resistant Hodgkin’s lymphoma (r/rHL). r/rHL has a high fatality rate and poor therapeutic prognosis. CD30 CAR-T-cell therapy has emerged as a new way to treat r/rHL in recent years. However, CD30CAR-T cells are still being explored in clinical trials. To help more patients, this review focuses on current CD30CAR-T-cell advancements as well as clinical breakthroughs in treatment of r/rHL.

Areas covered

This research examines the mechanism of action of CD30 CAR-T cells, their function in the real-world therapy of r/rHL, and the influence of different treatment regimens on treatment results.

Expert opinion

There has been much research into CD30 CAR-T cells as a result of their successful use in treatment of r/rHL. This research has helped us to understand CD30 CAR-T-cell safety as well as the management options available before and after its administration to increase patient survival and reduce side effects.

KEYWORDS:

• CD30 CAR-T
• relapsed or refractory hodgkin’s lymphoma
• pretreatment regimen
• maintenance theraty
• structural improvement

Article highlights

• The mechanism of CD30 CAR-T cells against tumor cells: The structural makeup of CD30, its mode of action, and the evolution and modifications in each generation of CAR-T are all covered in this section.

• Effectiveness and safety of CD30 CAR-T cells: This section explains the impact of CD30CAR-T cell therapy following its use in a clinic, demonstrating its efficacy and safety for r/rHL. It further explains that different CD30CAR-T dosages have different clinical efficacies, necessitating experimentation to determine the ideal dose level.

• Pretreatment regimen before CD30 CAR-T-cell therapy: This section explains the choice of pretreatment regimen prior to the administration of CD30CAR-T cell therapy. Current data indicates that fludarabine-based pretreatment regimens are better tolerated and significantly more effective in heavily pretreated r/rHL than other pretreatment regimens.

• Maintenance therapy after CD30 CAR-T: Following the administration of CD30CAR-T cell therapy, this section discusses several maintenance treatments. Different maintenance regimens have varying effects on prognosis, mostly through the use of anti-PD-1 therapy. After receiving anti-PD-1 medication, patients displayed an improved safety profile, which also increased the efficacy.

• CAR-T cells containing CD30 and other targets of r/rHL: The combination of anti-CD19 and CD30 dual-target CAR-Ts was used to treat a patient with r/rHL, who had r/r lymphoma with CD19 (+) and CD30 (+), and who had long-term PFS following treatment. This section describes the effect of CD30 CAR-T in combination with other target CAR-Ts acting together.

• Structural improvement of CD30 CAR-T cells: This section explains how alterations to CD30CAR-T cell structure can enhance anti-tumor effectiveness even more, boost durability, and lessen side effects. It also explains how the researchers enhanced the CD30CAR-T cells.

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.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial relationships or otherwise to disclose.

Additional information

Funding

This study was funded by the Key Research and Development Program of Shandong Province [No. 2018GSF118157], the National Natural Science Foundation [Grant No. 81400166] and the Key Research and Development Project of Jinan [No. 201907026].