EFFICIENT COST-EFFECTIVE MANUFACTURE OF A NON-VIRAL TRANSPOSON BASED NOVEL BAFF-CART FOR TREATMENT OF B-CELL CANCERS

Authors:
A.Lawrence, S.Kleinsorge-Block, L.Jonart, P.Caimi, R.Parameswaran, J.Reese
In:
Source: Cytotherapy
Publication Date: (2025)
Issue: S9: S243
Research Area:
Cancer Research/Cell Biology
Immunotherapy / Hematology
Gene Expression
Basic Research
Molecular Biology
Regenerative medicine
Drug Discovery
Cells used in publication:
T cell, human stim.
Species: human
Tissue Origin: blood
Platform:
4D-Nucleofector® LV-Unit
Experiment

We optimized the BAFF CART transposon-based manufacturing utilizing a 10-day process including enrichment of CD4 and CD8 T cells from a fresh leukapheresis (Miltenyi Biotec), followed by activation using TransAct™ (Miltenyi Biotec) and subsequent culture expansion in CTS OpTmizer™ media (Gibco) containing IL7 and IL15. The transposon was introduced using the 4D Nucleofector®-LV (Lonza).

Can be found under the following link: EFFICIENT COST-EFFECTIVE MANUFACTURE OF A NON-VIRAL TRANSPOSON BASED NOVEL BAFF-CART FOR TREATMENT OF B-CELL CANCERS - ScienceDirect

Abstract

CD19 CART cell therapies have shown remarkable efficacy in non-Hodgkin lymphoma. However, durable response has been observed in less than half of treated patients due to epitope loss and T cell exhaustion. To overcome this limitation, we developed a novel autologous BAFF-ligand based CART product (LMY-920) that targets BAFF receptors BAFFR/BR3, TACI and BCMA CAR-T capable of binding three different receptors, thereby minimizing the potential for antigen escape in the treatment of B cell cancers. Additionally, we improved manufacturing development time, cost, and efficiency using a novel TcBuster™ transposon system, which obviates the availability and cost hurdles associated with lentiviral vectors. GMP-grade transposon reagents can be generated in <4 months, the cost is lower than that of lentiviral vector and allows stable integration of >10K cargo.