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T-cell engagers (TCEs) activate T cells by binding both CD3 on T cells and tumor-specific antigens, enabling effective tumor cell killing. Initially successful in hematologic malignancies, TCEs are now advancing in solid tumors and autoimmune diseases. Recent studies at the AACR Annual Meeting showcased the latest progress and future potential of several TCEs.

QLS4131 (BCMA×GPRC5D×CD3) for Hematologic Malignancies

QLS4131 is a dual-target TCE developed for multiple myeloma, binding both BCMA and GPRC5D. Compared to similar agents like JNJ-79635322, QLS4131 shows significantly stronger tumor affinity and markedly more potent cytotoxicity. Early preclinical data supports its potential, with ongoing Phase 1 clinical trials.

Source: AACR Poster

Structure of QLS4131

Xaluritamig (STEAP1×CD3) for Solid Tumors

A 2+1 bispecific T-cell engager (TCE) targeting STEAP1 and CD3, xaluritamig has demonstrated initial safety and anti-tumor activity in patients with metastatic castration-resistant prostate cancer (mCRPC). Its efficacy appears independent of STEAP1 expression levels and common tumor genetic alterations, suggesting potential utility across a broad mCRPC population regardless of biomarker status.

https://investors.amgen.com/static-files/6d823d7d-2fd1-405a-8c0e-22aa91bee682

Structure of Xaluritamig

CC312 (CD19×CD28×CD3) for Autoimmune Diseases

CC312 is a trispecific antibody targeting CD19/CD28/CD3. In a humanized mouse model of systemic lupus erythematosus, it effectively depletes peripheral B cells and plasma cells, reducing IgG and anti-dsDNA levels, with no immune deposition or B cell infiltration in the kidneys. In ongoing clinical trials, even at the lowest dose (5 μg/dose), CC312 successfully clears peripheral B cells and subpopulations, with no ≥3 grade cytokine release syndrome or neurotoxicity observed. Some patients show improvement or remission, indicating promising therapeutic potential.

Source: CytoCares Official Website

Mechanism of Action of CC312

TCEs are continuously expanding therapeutic boundaries. In this process, high- consistency CD3 proteins are key tools to drug development. ACROBiosystems offers CD3E&CD3D, CD3E&CD3G, CD3E, CD3D, and CD3G protenis, supporting antibody screening and optimization to advance innovative therapies.

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