Limited efficacy of APRIL CAR in patients with multiple myeloma indicate challenges in the use of natural ligands for CAR T-cell therapy.

ABSTRACT:

Background

We used a proliferating ligand (APRIL) to construct a ligand-based third generation chimeric antigen receptor (CAR) able to target two myeloma antigens, B-cell maturation antigen (BCMA) and transmembrane activator and CAML interactor.

Methods

The APRIL CAR was evaluated in a Phase 1 clinical trial (NCT03287804, AUTO2) in patients with relapsed, refractory multiple myeloma. Eleven patients received 13 doses, the first 15×10⁶ CARs, and subsequent patients received 75,225,600 and 900×10⁶ CARs in a 3+3 escalation design.

Results

The APRIL CAR was well tolerated. Five (45.5%) patients developed Grade 1 cytokine release syndrome and there was no neurotoxicity. However, responses were only observed in 45.5% patients (1×very good partial respo

SUBMITTER: Lee L 

PROVIDER: S-EPMC10314698 | biostudies-literature | 2023 Jun

REPOSITORIES: biostudies-literature