Salt Lake City, Utah — February 4, 2026 — Leads & Copy — Arcellx, Inc. (NASDAQ: ACLX) has announced that a late-breaking abstract for its novel D-Domain binder in anitocabtagene autoleucel (anito-cel) has been accepted for presentation at the 2026 Tandem Meetings.
The poster (903) details a preclinical study exploring binder attributes’ role in the specificity of BCMA-directed CAR T cells. The Tandem Meetings are taking place from February 4-7, 2026, at the Salt Palace Convention Center in Salt Lake City, Utah.
CAR constructs representative of cilta-cel (dual VHH), ide-cel (scFv), and anito-cel (D-Domain) were assessed preclinically. Results showed no tonic signaling or off-target activity with the D-Domain binder, suggesting a favorable safety profile. CAR T activation and cytokine release, indicative of tonic signaling, were observed for dual VHH and scFv binders without BCMA antigen, but not with the D-Domain.
Off-target activity against Claudin-9 (CLDN9) was seen with the dual VHH binder, but not with the scFv binder or the D-Domain. Claudin-9 is a member of the Claudin family and is expressed at the tight junctions of endothelial and epithelial barriers. Binding of CLDN9 and BCMA could raise the risk of off-target toxicities. Claudin family proteins are involved in maintaining the structural and functional integrity of the blood–brain and gut–vascular barriers, and disrupted Claudin function is linked to inflammatory, neurodegenerative, and gut disorders.
The presentation copy can be found on Arcellx’s website at www.arcellx.com under the Pipeline/Scientific publications section.
Alexandra Witter, PhD, will be the speaker. The session, titled “Poster Session: Late-Breaking Poster Abstracts”, will be held Thursday, February 5, 2026, from 6:30 – 8:00 p.m. MT in Hall AB.
BCMA-directed CAR T therapies are effective in treating relapsed and/or refractory multiple myeloma, with the potential for deep and durable responses. Anitocabtagene autoleucel (anito-cel) has demonstrated encouraging efficacy and safety, with no cases of delayed neurotoxicities or immune effector cell-associated enterocolitis (IEC-EC) observed to date (Patel et al., ASH 2025). This profile differentiation may be attributable to the different BCMA-targeting binders used in these CAR-T cell therapies, as current standard-of-care BCMA-directed CAR-T cell therapies either demonstrate suboptimal efficacy with idecabtagene vicleucel (ide-cel), or a risk of delayed toxicities such as parkinsonism, cranial nerve palsies or IEC-EC with ciltacabtagene autoleucel (cilta-cel). Anito-cel utilizes a novel synthetic D-Domain binder, with binding to BCMA characterized by a fast off-rate and displays minimal antigen-independent aggregation (Hart et al., ASH 2025).
The study aimed to explore the contribution of binder attributes towards specificity of BCMA-directed CAR-T cells.
Researchers transduced CAR constructs representative of cilta-cel (dual VHH), ide-cel (scFv) and anito-cel (D-Domain) into healthy donor T cells. Key attributes such as phenotypes associated with tonic signaling and target-specific activity were compared between surrogate CAR-T cells with matched CAR-positive frequency and vector copy number.
Dual VHH CAR-T cells show increased expression of FAS, ICAM and TRAIL, compared to D-Domain CAR-T cells, in the absence of antigen-expressing cells suggesting a tonic signaling phenotype. D-Domain CAR-T cells did not show expression of activation markers (CD69, 4-1BB) or IFNγ release, which were elevated 3-fold and 39-fold respectively, with dual VHH CAR-T cells. As previously reported from a membrane surface protein array, cilta-cel bound to Claudin-9 (CLDN9) in addition to BCMA (EPAR EMA/594558/2022, EMA 2022).
CLDN9-induced activity was not observed with D-Domain or scFv CAR-T cells under any conditions tested.
The company says off-target activity with dual VHH CAR-T cells was seen against CLDN9, suggesting that the high avidity dual VHH binder could recognize other cryptic epitopes and lead to off-tumor binding and toxicities. The D-Domain exhibits favorable features such as stability and rapid off-rate differentiating it from the dual VHH binder, which may contribute to the enhanced target specificity and lack of tonic signaling described here.
Anitocabtagene autoleucel (anito-cel, previously CART-ddBCMA) is the first BCMA-directed CAR T-cell therapy to be investigated in multiple myeloma that utilizes Arcellx’s novel and compact binder known as the D-Domain. Anito-cel has been granted Fast Track, Orphan Drug, and Regenerative Medicine Advanced Therapy Designations by the U.S. Food and Drug Administration.
Arcellx and Kite, a Gilead Company, have a global strategic collaboration and license agreement to co-develop and co-commercialize anito-cel for patients with multiple myeloma. Kite and Arcellx will jointly commercialize the anito-cel asset in the United States, and Kite will commercialize the product outside the United States. Anito-cel is currently being developed in a Phase 2 registrational pivotal study and a global Phase 3 randomized controlled study for relapsed and/or refractory multiple myeloma (RRMM).
Arcellx, Inc. is focused on delivering a new class of innovative immunotherapies for patients with cancer and other incurable diseases.
Source: Arcellx, Inc.
