Targeting Two B-Cell Markers at Once AbelZeta’s Bispecific CAR-T for Autoimmune Disease and Blood Cancer

Chimeric antigen receptor (CAR) T-cell therapy has demonstrated remarkable efficacy in B-cell cancers, and is now being explored for severe autoimmune diseases. A divisional patent from AbelZeta Inc. describes a bispecific CAR that simultaneously targets two distinct B-cell surface markers – CD20 and BCMA – with the aim of achieving more complete B-cell and plasma cell depletion than single-target approaches.

The Problem

Autoimmune diseases such as systemic lupus erythematosus (SLE) are characterised by aberrant B-cell activity: autoreactive B cells produce antibodies against the body’s own tissues, while long-lived plasma cells (LLPCs) maintain this pathological response even after B-cell depletion. The challenge in treating SLE and related conditions is that different pathogenic cell types express different surface markers.

Naïve B cells and memory B cells that produce anti-DNA autoantibodies maintain high expression of CD20. However, the long-lived plasma cells responsible for producing anti-RNA-binding protein antibodies lose CD20 expression as they mature, while gaining expression of BCMA (B-cell maturation antigen), a marker present on all mature plasma cells.

Anti-CD20 antibody therapies such as rituximab have shown promise in open-label SLE trials but failed to meet primary endpoints in randomised controlled trials, likely because they cannot eliminate BCMA-positive LLPCs. A CAR-T approach that can target both CD20-positive B cells and BCMA-positive plasma cells simultaneously would offer a more comprehensive depletion strategy than either target alone. The same dual targeting logic applies to haematological cancers such as multiple myeloma, where both CD20 and BCMA are expressed on malignant cells.

What This Invention Does

The bispecific CAR described in this patent incorporates two separate antigen-binding domains within a single CAR construct. The first is an anti-CD20 scFv (single-chain variable fragment) comprising light chain variable region VL1 and heavy chain variable region VH1, with CDR sequences approximately 80-100% identical to those defined in the sequence listing. The second is an anti-BCMA scFv comprising VL2 and VH2, with similarly defined CDR sequences.

The bispecific CAR further comprises a signal peptide, a hinge region (from IgG4, CD8, CD28, or CD137), a transmembrane domain (from CD8, CD28, or other T-cell surface proteins), a co-stimulatory region (from 4-1BB/CD137, CD28, OX40, or other costimulatory molecules), and a cytoplasmic signalling domain from CD3 zeta. The complete bispecific CAR construct includes defined full-length amino acid sequences (SEQ ID No. 26, 40, 54, 68, 84, 98, 112, or 126).

The CAR can be expressed in T cells or natural killer (NK) cells. T cells engineered to express the bispecific CAR are able to recognise and eliminate cells expressing either CD20 or BCMA, or both, enabling simultaneous depletion of B cells and plasma cells from a single therapeutic product.

Key Features

Dual antigen targeting. A single CAR construct carries antigen-binding domains for both CD20 and BCMA, enabling CAR-T cells expressing it to recognise and eliminate both B cells (CD20-positive) and plasma cells (BCMA-positive) without requiring two separate cell therapy products.

scFv-based binding domains. Both the anti-CD20 and anti-BCMA binding regions are scFvs, each comprising a linked heavy and light chain variable region pair, with defined CDR sequences providing specificity for their respective targets.

Flexible domain architecture. The hinge, transmembrane, and co-stimulatory domains can be selected from a range of validated options, allowing the CAR structure to be tuned for different immune cell types and clinical contexts.

4-1BB and CD28 co-stimulation options. The co-stimulatory domain can be drawn from 4-1BB, CD28, OX40, or other molecules known to support durable T-cell activation, persistence, and memory formation.

Applications in autoimmunity and cancer. The bispecific CAR is described for use in treating autoimmune disorders including SLE, lupus nephritis, rheumatoid arthritis, and multiple sclerosis, as well as haematological malignancies such as multiple myeloma and B-cell lymphoma.

Who Is Behind It?

The applicant is AbelZeta Inc., a US-based cell therapy company. The named inventors are Yao Yihong, Huang Jiaqi, Zhu Shigui, Yao Xin, Luo Xiaobing, and Wei Yutian. This divisional was filed on 26 February 2026, derived from parent application AU 2024244733, filed 29 March 2024, which traces to US Provisional Patent Application 63/493,495 (filed 31 March 2023) and 63/509,371 (filed 21 June 2023). Phillips Ormonde Fitzpatrick in Melbourne are the Australian patent attorneys.

Why It Matters

The treatment of severe autoimmune diseases with CAR-T cell therapy represents one of the most exciting developments in clinical immunology. Early compassionate-use results with CD19 CAR-T cells in refractory SLE have shown deep and durable B-cell depletion with drug-free remission in some patients. However, the incomplete depletion of BCMA-positive long-lived plasma cells may limit the durability of CD19 or CD20-only CAR approaches. A bispecific CAR that can simultaneously eliminate both B-cell compartments – the CD20-positive naïve and memory B cells and the BCMA-positive plasma cells – has the potential to achieve more complete and sustained disease remission.

Given that SLE affects approximately 5 million people worldwide, many of whom are refractory to existing immunosuppressive therapies, and that multiple myeloma remains largely incurable with conventional treatment, the commercial and clinical significance of an effective bispecific CAR-T therapy is substantial.

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AU 2026201441 was published in the Australian Official Journal of Patents on 19 March 2026 and is open for public inspection. Patent applications represent inventions that are sought to be protected and do not necessarily reflect commercially available products.

Related Concepts

CAR T-cell therapy engineers a patient’s own T cells to express a synthetic receptor that directs them to kill tumour cells or pathogenic immune cells. Bispecific CARs extend this approach by incorporating two antigen-binding domains in a single construct, enabling simultaneous targeting of distinct cell populations without requiring two separate therapies.

In systemic lupus erythematosus, autoreactive plasma cells expressing BCMA are invisible to CD20-directed therapies such as rituximab, making dual targeting strategies an important frontier in autoimmune therapy.