Singapore scientists and clinicians have discovered a promising use of antibodies to target a new cancer antigen, as an alternative for chemotherapy.

Scientists from A*STAR’s Institute of Molecular and Cell Biology (IMCB) have discovered an immunotherapy that could potentially be used to treat common cancers. They generated PRL3-zumab, a humanised antibody[1] to target the PRL-3 protein, a tumour antigen that promotes cancer growth and is found in about 80 per cent of 11 common cancers the researchers examined. Using antibodies to attack cancer cells in the body is a form of cancer immunotherapy that harnesses the immune system to kill cancer cells. By targeting the tumour specific antigen PRL-3; the PRL3-zumab humanised antibody could be used to develop targeted cancer treatments with advantages over chemotherapy and its disruptive side effects. It does so by not damaging surrounding healthy cells that do not express PRL-3. These findings were published in leading scientific journal Nature Communications on 6 June 2019.

Using animal models initially, the IMCB research team found that the PRL-3 mouse antibody could suppress tumour growths that expressed the PRL-3 antigen in gastric, liver, lung, ovary, breast, acute myeloid leukaemia (AML) and kidney cancers. Since 2012, the IMCB research team has been working in collaboration with clinician researchers from the Department of Haematology-Oncology at the National University Cancer Institute, Singapore (NCIS); National University Hospital’s Tissue Repository (NUHS-TR); National Cancer Centre Singapore; Singapore General Hospital; Lee Kong Chian School of Medicine at Nanyang Technological University; Cancer Science Institute of Singapore, National University of Singapore; and Yong Loo Lin School of Medicine, National University of Singapore, to test the PRL3 protein expression on human tumour samples. The study could support PRL3-zumab as a first-in-class humanised antibody to be potentially used as a drug against a broad spectrum of tumours expressing PRL-3. These common cancers include those of the liver, lung, gastric, breast, colon, and kidney.

“PRL3-zumab represents an innovative and disruptive approach to cancer therapy, as it is highly targeted to cancer cells and has less side effects compared to traditional cancer drugs. It was conventionally perceived that antibodies cannot be used to target intracellular oncotargets due to their inability to cross cellular membranes. However, we discovered that the intracellular PRL3 oncotarget could be externalised on the surface of cancer cells to be targeted by antibodies to trigger the host’s immune system. This discovery opens a new avenue for cancer immunotherapy for a spectrum of intracellular oncotargets,” said Professor Qi Zeng, Research Director at A*STAR’s IMCB and lead researcher of the study.

A*ccelerate, A*STAR’s commercialisation arm, has patented Prof Qi Zeng’s concept globally since 2008. Prof Qi Zeng has also set up A*STAR spin-off Intra-ImmuSG Pte Ltd in 2015 to further develop PRL3-zumab for clinical use.

In 2018, PRL3-zumab completed Phase 1a and 1b clinical trials in solid tumours at the National University Cancer Institute, Singapore. Moving forward, the drug is also undergoing Phase 1b extension in liquid cancers (such as AML and multiple myeloma) at NCIS, monitored by Singapore Clinical Research Institute (SCRI). Furthermore, PRL3-zumab will soon be undergoing Phase 2 clinical trials at the National Cancer Centre Singapore (NCCS) to test the efficacy of PRL3-zumab against broader types of solid tumours. Phase 1 evaluates the safety and tolerability of PRL3-zumab in advanced solid tumours patients, while Phase 2 will test for efficacy and proof of concept of the therapy.


For more information, please refer to the paper “PRL3-zumab as an immunotherapy to inhibit tumors expressing PRL3 oncoprotein”, published online by the journal Nature Communications on 6 June 2019.

Link to paper: https://www.nature.com/articles/s41467-019-10127-x

 

[1] Antibodies from non-human species whose protein sequences have been modified to increase their similarity to antibody variants produced naturally in humans.

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