Neuroendocrine tumors (NETs) pose significant challenges in current treatments due to their high heterogeneity and complexity. SEZ6 (Seizure-related 6 homolog), a key regulator of dendritic formation and neural signaling, plays an important role in NETs, particularly in small cell lung cancer (SCLC). Studies have shown that SEZ6 is overexpressed in SCLC and is closely associated with tumor cell proliferation and invasion, making it a potential therapeutic target. Currently, antibody-drug conjugates (ADCs) targeting SEZ6 have shown promising results in preclinical studies, offering a potential new precision treatment option for NET patients in the future.

ABBV-706: Intended for the Treatment of Relapsed/Refractory SCLC

AbbVie’s ABBV-706 is an ADC targeting SEZ6, linked to the topoisomerase 1 inhibitor (TOP1i) payload via a valine-alanine linker, with a drug-to-antibody ratio (DAR) of 6. ABBV-706 specifically targets SEZ6-expressing tumor cells, rapidly internalizes, and delivers the cytotoxic TOP1i payload. It has demonstrated significant antiproliferative activity across various SCLC cell lines and sustained tumor regression in SCLC PDX models. Currently in Phase 1 clinical trials, ABBV-706 is being evaluated both as a monotherapy and in combination with the PD-1 inhibitor Budigalimab (ABBV-181), as well as with carboplatin or cisplatin. As the only SEZ6-targeting ADC in development for SCLC, ABBV-706’s progress is drawing significant industry attention.

SEZ6-ADC Mechanism of Action

(Image Source: AbbVie Official Website, https://www.abbvie.com)

At the May 2024 ASCO meeting, AbbVie presented early data from the first-in-human dose-escalation study of ABBV-706 monotherapy. The results showed an overall objective response rate (ORR) of 43.8% among 48 evaluable patients, with 60.9% in the SCLC group and 28% in the NET group. As of the data cutoff, the most common Grade ≥3 treatment-emergent adverse events (TEAEs) included neutropenia (42%), anemia (42%), and leukopenia (28%). These findings provide strong support for ABBV-706 as a potential treatment option. On July 25, 2024, China’s Center for Drug Evaluation (CDE) approved AbbVie’s clinical trial application for ABBV-706 lyophilized powder for injection. Subsequently, on October 29, 2024, the U.S. Food and Drug Administration (FDA) granted orphan drug designation (ODD) to ABBV-706 for the treatment of SCLC. This designation highlights ABBV-706’s potential in treating this rare and highly aggressive cancer and further validates SEZ6 as an effective therapeutic target for SCLC.

ADC Therapy: The Future of SCLC Treatment

SCLC accounts for approximately 15% of all lung cancers and is characterized by high malignancy, rapid progression, and a high recurrence rate, making it challenging to treat. Currently, chemotherapy and radiotherapy remain the primary treatment options, but they offer limited survival benefits and poor prognosis. Exploring novel targeted therapies is the future direction to enhance treatment efficacy and improve patient survival.

ADC Mechanism of Action and Drug Development Target for SCLC ¹

BCompared to traditional chemotherapy and radiotherapy, ADC drugs offer significant advantages in treating refractory/relapsed SCLC. ADCs can precisely target specific antigens found in SCLC, reducing damage to normal cells while enhancing cytotoxic effects. They overcome chemotherapy resistance and provide new treatment options for recurrent tumors, significantly improving efficacy and patient survival. Additionally, due to the dual-targeting nature of bispecific antibodies, which target two different antigens or pathological targets to enhance immune response, overcome treatment resistance, and improve tumor clearance. Recently, pharmaceutical companies have been exploring combinations of ADCs with bispecific antibodies targeting SCLC-related antigens like DLL3 to achieve better therapeutic outcomes.

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High-Quality SEZ6 Tools Support SCLC Drug Development

ACROBiosystems launches a series of high-quality biopharmaceutical development tools covering SEZ6 recombinant proteins and SEZ6 stable cell line, meeting the ADC development needs for SCLC.

•  SEZ6 recombinant proteins: Both are expressed in human-derived cells HEK293 and validated by SDS-PAGE, SEC-MALS, ELISA, SPR, featuring high purity, high activity, high batch-to-batch consistency. They are suitable for applications in immunization, antibody screening, and candidate drug functional validation.

•  SEZ6 stable cell lines: The stable cell lines for SEZ6 antigen stably expresses the protein on the surface of host cells for long-term use. Supports antibody drug activity screening (cell-level binding and blocking) and evaluating CAR molecule cytotoxicity, providing essential tools for drug development and functional testing.

•  A variety of high-quality targeted drug development tools for SCLC, including DLL3、CD56、TROP2、B7H3、c-MET、HER2、PD-1/PD-L1 are also available, fully supporting your drug development research!

ACROBiosystems performs batch-to-batch quality control on all products, verifying properties such as purity and binding activity, and provides free protocols to streamline SEZ6-targeted drug development.