In brief

Researchers find that PRL3, a cancer-specific protein in adult patients, is differentially expressed in paediatric tumours. In a first-in-child, compassionate trial of novel humanised antibody PRL3-zumab, the drug specifically targeted cancer cells and improved clinical outcomes.

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Targeted therapy sparks childhood cancer hope

4 Mar 2024

An experimental antibody therapy for solid tumours in adults also shows promise in improving quality of life for paediatric patients.

The quest for effective cancer treatments has long been hampered by a crucial limitation: conventional approaches like chemotherapy can’t differentiate between healthy and cancerous cells. This lack of specificity can damage healthy tissues along the way and trigger debilitating adverse effects.

According to Qi Zeng, a Research Director at A*STAR’s Institute of Molecular and Cell Biology (IMCB), asserted that the crux of advancing cancer treatment lies in identifying molecular targets that are exclusively associated with tumours. This precision is especially critical for young children with cancer, who can be more vulnerable than adult patients.

In 1998, Zeng and colleagues first discovered PRL3: a cancer-specific protein that controls various cellular processes. As they traced PRL3‘s footsteps over the years, they found that it contributed to the spread of malignant cells in many different cancer types.

“Our lab has studied hundreds of adult tumour samples. We’ve found that approximately 80.6 percent of tumours in adults express PRL3, while adjacent normal tissue does not,” said Zeng.

The team also pioneered the discovery of PRL3-zumab, the first humanised antibody therapy against PRL3, which showed a promising safety profile in adults during a clinical trial in 2017.

In their latest study, Zeng and IMCB colleague Min Thura teamed up with Amos Hong Pheng Loh, Shui Yen Soh and other experts from the KK Women’s and Children’s Hospital, Singapore and Duke-NUS Medical School, Singapore, to investigate the use of PRL3-zumab in treating paediatric cancers.

By analysing 65 tumour-derived and healthy tissues from paediatric patients, the researchers found that PRL3 was frequently expressed in soft tissue tumours in the muscles and kidneys, and in all neuroblastomas studied. Significantly, the presence of PRL3-positive tumours correlated with heightened angiogenesis—the creation of blood vessels that support tumour growth and metastasis.

Spurred by these findings, the team was optimistic that PRL3-zumab might be as effective for children as it is in adults. “We did a first-in-child compassionate use trial of PRL3-zumab,” said Zeng, adding that the treatment was administered to a seven-year-old in critical condition with recurrent rhabdomyosarcoma, a soft tissue cancer.

The team reported that PRL3-zumab, in combination with radiation therapy, temporarily stabilised the child’s condition, prolonged his life by three months and enhanced his quality of life even in an advanced stage of cancer. “The boy was off morphine and supplemental oxygen; he left the ICU to return home, and was even able to go to school for three days,” Zeng recalled.

These outcomes support further exploration of PRL3 expression as a prognostic cancer biomarker, as well as PRL3-zumab use in paediatric patients with aggressive cancers who have exhausted all standard options, Zeng said.

In December 2015, Zeng founded the spinoff biotech company Intra-ImmuSG, which is currently conducting phase 2 clinical trials with PRL3-zumab for adults with cancer in Singapore, China, the US and Malaysia.

The A*STAR-affiliated researchers contributing to this research are from the Institute of Molecular and Cell Biology (IMCB).

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Loh, A.H.P., Thura, M., Gupta, A., Tan, S.H., Kuan, K.K.Y., et al. Exploiting frequent and specific expression of PRL3 in pediatric solid tumors for first-in-child use of PRL3-zumab humanized antibody. Molecular Therapy Oncology 30, 153-166 (2023). | article

About the Researcher

Qi Zeng is presently Research Director at A*STAR’s Institute of Molecular Cell Biology (IMCB). She is also Adjunct Professor at the Department of Biochemistry of the National University of Singapore (NUS). Zeng carried out her PhD research at Roswell Park Memorial Institute (RPMI, US) and IMCB and was conferred her PhD degree by NUS in 1993. Later, her team demonstrated that PRL1 and PRL3 monoclonal antibodies inhibit experimental metastatic tumours expressing these antigens. She is a pioneer in using the unconventional approach of immunotherapy to target intracellular oncoproteins for inhibiting tumour growth in mouse models of cancer.

This article was made for A*STAR Research by Wildtype Media Group