Clinical Strategies for Enhancing the Efficacy of CAR T-Cell Therapy for Hematological Malignancies

Abstract

Chimeric antigen receptor (CAR) T cells have been successfully used for hematological malignancies, especially for relapsed/refractory B-cell acute lymphoblastic leukemia and non-Hodgkin’s lymphoma. Patients who have undergone conventional chemo-immunotherapy and have relapsed can achieve complete remission for several months with the infusion of CAR T-cells. However, side effects and short duration of response are still major barriers to further CAR T-cell therapy. To improve the efficacy, multiple targets, the discovery of new target antigens, and CAR T-cell optimization have been extensively studied. Nevertheless, the fact that the determination of the efficacy of CAR T-cell therapy is inseparable from the discussion of clinical application strategies has rarely been discussed. In this review, we will discuss some clinical application strategies, including lymphodepletion regimens, dosing strategies, combination treatment, and side effect management, which are closely related to augmenting and maximizing the efficacy of CAR T-cell therapy.

Nanobody-based chimeric antigen receptor (NbCAR) T cells for in-vivo cancer immunotherapy: A systematic review

“…An et al (13) developed NbCAR T cells against CD38 and designed a study to treat multiple myeloma xenograft mice with these NbCAR T cells. Tumor reached 2455 mm 3 (P<0.05) in mice treated with CD38 Nb CAR T cells after 65 days of follow-up, whereas the tumor size in mice treated with either PBS or mock-T cells was 5669 mm 3 and 5260 mm 3 , respectively. The survival rate was not reported in this study.…”

“…De Munter et al (36) designed two groups of mice transplanted with either THP-1 cells or RL tumor cells and treated them with CD33 and CD20 NbCAR T cells, respectively. Following CD20-1-4_1BB:ζ nanoCAR treatment of mice bearing RL cells, the tumor was eradicated till 38 days of follow-up (P<0.05), while in the control group (PBS treatment), tumor reached a size of 293 mm 3 . In mice transplanted with THP-1 cells, treatment with CD33-1-4_1BB: ζ nanoCAR prolonged the survival up to 35 days (P< 0.05), whereas in the PBS group, survival was 14 days.…”

“…This feature allows cytotoxic T cells to overcome recognition problems associated with restricted MHC presentation on the surface of tumor cells (2). Briefly, CAR-T cells are manufactured by harvesting T-cells from a patient's blood, activating harvested T cells, and introducing the CAR gene to cells by various methods, including retroviral or lentiviral vectors.These transduced CAR-T cells are then expanded in-vitro and administrated to the patient intravenously, often after lymphodepletion with cyclophosphamide (CP) or fludarabine (Flu) (3).…”

The Future Directions of CAR-T Cell Therapy: Unlocking the Potential of Immunotherapy in Cancer Treatment

“…CD20, overexpressed in most B cell lymphomas, has shown promise as a target, with anti-CD20 CAR-T cell therapy achieving an overall response rate of 86% in early clinical trials [27]. To prevent antigen escape, a combination of anti-CD19 and anti-CD20 CAR-T cells has been investigated and found to be safe and feasible [1,28,29]. CD22, highly expressed on most B cell malignancies but not on hematopoietic stem cells, is another promising target, with anti-CD22 CAR-T cell therapy showing excellent efficacy in patients who have failed previous anti-CD19 CAR-T cell therapy [1,30].…”