A new immunotherapy strategy targeted CD30 in peripheral T-cell lymphomas: CAR-modified T-cell therapy based on CD30 mAb

Abstract

Chimeric antigen receptor T-cell immunotherapy (CAR-T) has shown remarkable efficacy in treating tumors of lymphopoietic origin. Herein, we demonstrate an effective CAR-T cell treatment for recurrent and malignant CD30-positive peripheral T-cell lymphomas (PTCL) has been demonstrated. The extracellular fragment gene sequences of CD30 were obtained from tumor tissues of PTCL patients and cloned into a plasmid vector to express the CD30 antigen. The CD30 targeting single-chain antibody fragment (scFv) was obtained from CD30-positive monoclonal hybridoma cells, which were obtained from CD30 antigen immunized mice. After a second-generation of CAR lentiviral construction, CD30 CAR T cells were produced and used to determine the cytotoxicity of this construct toward Karpas 299 cells. The results of CD30 CAR T-mediated cell lysis show that 9C11-2 CAR T cells could significantly promote the lysis of CD30-positive Karpas 299 cells in both LDH and real-time cell electronic sensing (RTCA) assays. In vivo data show that 9C11-2 CAR T cells effectively suppress the tumor growth in a Karpas 299 cell xenograft NCG mouse model. The CD30 CAR T cells exhibited an efficient cytotoxic effect after being co-cultured with the target cells and they also exhibited a significant tumor-inhibiting ability after being intravenously injected into PTCL xenograft tumors; these observations suggest that the new CD30 CAR-T cell may be a promising therapeutic candidate for cancer therapy.

Methyl Donors Reduce Cell Proliferation by Diminishing Erk-Signaling and NFkB Levels, While Increasing E-Cadherin Expression in Panc-1 Cell Line

“…CD30 is a rediscovered target of new immunotherapies in non-lymphomatous solid tumors [ 43 ]. It triggers anti-apoptotic and pro-survival functions [ 44 ] through partly activating the NFkB pathway as well as mitogen-activated protein kinase (MAPK) pathways, including ERK1 and ERK2 [ 45 ].…”

CAR-T Cell Therapy in Hematological Malignancies: Current Opportunities and Challenges

“…Thus, CD30 is an ideal target for these lymphoma subtypes, and the anti-CD30 antibody-drug conjugate brentuximab vedotin (BV) has shown a high response rate in newly diagnosed PTCL patients (38,39). Given the encouraging clinical efficacy of BV, the anti-CD30 CAR-T cells were developed and exhibited remarkable cytotoxicity against CD30 positive lymphomas in preclinical studies (40,41).…”

CD30 as a therapeutic target in adult haematological malignancies: Where are we now?

“…Anti-CD30 CAR-T cells have been shown to have an efficient cytotoxic effect when cocultured with target cells and to display significant anti-tumour effects after injection into peripheral T-cell lymphoma (PTCL) xenograft tumours. 69 CAR-T cell-based combinations have also been considered. One phase II clinical trial combined a single dose of anti-CD30 CAR-T cells with an anti-PD1 Ab administered 14 days later and then every 3 weeks thereafter, in patients with CD30 + lymphomas, after lymphodepletion with fludarabine and cyclophosphamide.…”