Related Experiment Video
Updated: May 29, 2026
Stereotactic Adoptive Transfer of Cytotoxic Immune Cells in Murine Models of Orthotopic Human Glioblastoma Multiforme Xenografts
Published on: September 1, 2018
Genetically engineered humanized anti-ganglioside GM2 antibody against multiple organ metastasis produced by
Tadaaki Yamada1, Hideaki Bando, Shinji Takeuchi
1Division of Medical Oncology, Cancer Research Institute, Kanazawa University, Ishikawa, Japan.
Abstract:
Small-cell lung cancer (SCLC) grows rapidly and metastasizes to multiple organs. We examined the antimetastatic effects of the humanized anti-ganglioside GM2 (GM2) antibodies, BIW-8962 and KM8927, compared with the chimeric antibody KM966, in a SCID mouse model of multiple organ metastases induced by GM2-expressing SCLC cells. BIW-8962 and KM8927 induced higher antibody-dependent cellular cytotoxicity and complement-dependent cytotoxicity than KM966 against the GM2-expressing SCLC cell line SBC-3 in vitro. These humanized antibodies inhibited the production of multiple organ metastases, increased the number of apoptotic cells, and prolonged the survival of the SCID mice. Histological analyses using clinical specimens showed that SCLC cells expressed GM2. These findings suggest that humanized anti-GM2 antibodies could be therapeutically useful for controlling multiple organ metastases of GM2-expressing SCLC.
Insights
Humanized anti-ganglioside GM2 (GM2) antibodies effectively reduced metastasis in small-cell lung cancer (SCLC) models. These antibodies demonstrated superior cytotoxicity and prolonged survival in mice, suggesting therapeutic potential for SCLC. Keywords: anti-GM2 antibodies, SCLC metastasis, immunotherapy.
Area of Science:
- Oncology
- Immunology
- Cancer Research
Background:
- Small-cell lung cancer (SCLC) is characterized by rapid growth and frequent metastasis.
- Ganglioside GM2 (GM2) is expressed on SCLC cells and is a potential therapeutic target.
- Metastasis to multiple organs remains a significant challenge in SCLC patient outcomes.
Purpose of the Study:
- To evaluate the antimetastatic efficacy of humanized anti-GM2 antibodies (BIW-8962, KM8927) compared to a chimeric antibody (KM966).
- To assess the in vitro cytotoxicity and in vivo antimetastatic effects in a preclinical SCLC model.
- To investigate the expression of GM2 in clinical SCLC specimens.
Main Methods:
- Utilized a severe combined immunodeficient (SCID) mouse model with GM2-expressing SCLC cells to induce multiple organ metastases.
- Performed in vitro assays to compare antibody-dependent cellular cytotoxicity (ADCC) and complement-dependent cytotoxicity (CDC) of anti-GM2 antibodies against the SBC-3 SCLC cell line.
- Conducted histological analyses on clinical SCLC specimens to confirm GM2 expression.
Main Results:
- Humanized anti-GM2 antibodies BIW-8962 and KM8927 exhibited significantly higher ADCC and CDC compared to the chimeric antibody KM966 in vitro.
- Treatment with humanized anti-GM2 antibodies effectively inhibited the development of multiple organ metastases in the SCID mouse model.
- These antibodies increased tumor cell apoptosis and significantly prolonged the survival of treated mice.
- GM2 expression was confirmed in SCLC cells from clinical specimens.
Conclusions:
- Humanized anti-GM2 antibodies demonstrate potent antimetastatic activity against GM2-expressing SCLC.
- The enhanced in vitro cytotoxicity translates to significant in vivo efficacy in reducing metastasis and improving survival.
- These findings support the potential of humanized anti-GM2 antibodies as a novel therapeutic strategy for controlling SCLC metastasis.
