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COLUMNS
Making Strides Against Liver Cancer With Transformative Cellular Therapy
Cancer is one of the leading causes of death in the world and arguably the most heart-wrenching. In Singapore, liver cancer is the third deadliest cancer among men and the fifth among women. In fact, according to the Global Cancer Observatory, it is estimated that by 2040, the number of deaths caused by liver cancer will likely double.

Yet, many still hold out hope for an increased chance at survival or perhaps a less painful end.

by Christy Ma

SCG Looking To Prevent Infections Before Cancers

Infection is one of the major causes of cancer and liver cancer is no different. In Asia, the majority of liver cancer starts from the Hepatitis B virus (HBV), which attacks the liver and causes chronic diseases. About 10–20 per cent of the Asian population is infected with the Hepatitis B virus (HBV). Further, HBV patients make up 80 per cent of liver cancer patients, making HBV the leading cause of this cancer in the region.

The silver lining is that if detected early, there are more curative treatment options for liver cancer patients, which provides a higher chance of long-term survival. However, it is challenging to detect liver cancer early due to the negligible symptoms that appear until cancer develops into later stages. For example, small liver tumours are usually undetectable during a physical exam because the position of our livers in our bodies is naturally concealed by the right rib cage. So by the time a tumour is detected, it might have already become quite advanced.

Further to that, there are currently no widely recommended screening tests for liver cancer. What is more concerning here is that there are limited available treatments in the market right now for patients who are at advanced cancer stages. What’s more, such treatments only guarantee a 3 per cent of five-year relative survival rate, a far cry from what patients would expect after spending exorbitant amounts of money on such treatments.

While there are multiple treatments like target therapies or stem cell transplants available to treat other forms of cancers, what may work for one cancer type may not be as effective for others (as cancers vary depending on the tissue of origin). This is why innovative biotech companies like SCG Cell Therapy (SCG) are studying and developing a cure to identify new ways to treat cancer and eradicate the virus before cancers can develop.

In recent years, a new form of immunotherapy treatment called “cellular therapy” has emerged. This form of treatment modifies a patient’s self-immune cells to be more effective at detecting and destroying cancer cells. Such technology has advanced cancer treatments and could possibly be the answer to the world’s plea for a better cure.

The Newest Cellular Therapy for Liver Cancer

Cellular therapy was a niche treatment that was once deemed far-fetched. Even after its entrance into the international market back in 2017, it is still considered an early innovation in Singapore. While positioned as a revolutionary living drug to treat cancer, cellular therapy is currently only available for haematologic malignancies, more commonly known as blood cancer. In fact, the first group of patients in Singapore to receive cell therapy did so less than a year ago in September 2021 for leukaemia and lymphoma.

Only a handful of companies in Singapore are working on developing a cure for liver cancer through cellular therapy. SCG, a Singapore-based biotech company, recognises these gaps in the medical industry, which is why SCG has been advancing cellular therapy, namely a T-Cell Receptor Transduced T-cells (TCR-T) therapy, to further increase the efficacy of current standard antitumour therapies.

As its name suggests, cellular therapy uses cells to fight cancer. Our bodies have circulating immune cells called T-cells that carry their own proteins called T-cell receptors, which detect foreign antigens. Once T-cells receptors bind to foreign antigens, it will trigger signalling cascades that activate the immune system to eliminate the foreign substance. However with cancers, our T-cells are unable to detect these foreign cancerous antigens, hence there’s a need for T-cells redirection and T-cell receptor reconfiguration.

By modifying T-cells through genetic engineering in a laboratory, and reinjecting them back into the patient’s body (also known as autologous cellular therapy), the engineered T-cells are able to recognise and target cancer cell antigens better than before, enhancing the T-cells’ fighting power to attack cancer cells. Arising from the success of cell therapy in haematologic malignancies, T-cell receptor engineered T-cells (TCR-T) in solid tumours have become a hot topic in cancer research, including liver cancer studies. To date, there are a handful of TCR-T cell therapy products in clinical trials worldwide and SCG101 TCR-T cell therapy is one of them.

Promising Clinical Trials of SCG101 by SCG Cell Therapy

What is unique with SCG101 TCR-T is that it can redirect T-cells specifically against the HBV antigen not only to target and eliminate HBsAg-positive cancer cells but also to eradicate HBV cccDNA (covalently closed circular DNA), which is the intracellular viral replication machinery that causes persistent HBV infection. Therefore, SCG101 addresses both the antitumour immune response and promises antiviral activity to eradicate chronic HBV infection – one of the primary drivers of liver cancer in Asia.

What’s more, SCG101 released the first clinical proof-of-concept earlier this year, which has never been seen before dual antiviral and antitumour activities. The proof-of-concept shows improved tumour control and lesion shrinkage in two out of three patients (66 per cent) with advanced HBV-related HCC. Bolstered by the favourable results, Phase I/II trials with SCG101 for HBV-related liver cancer are currently underway.

On top of that, SCG101 also boasts the first-in-the-world cellular therapy treatment that has been approved to conduct multi-country clinical trials in China, Singapore, and the U.S. This helps in progressing SCG101 to the next stage of the clinical trials, making strides closer to finding a cure for liver cancer through cellular therapy.

In Singapore, SCG collaborates with the Cell Therapy Facility of Singapore Health Science Authority to utilise the most sophisticated closed and automated technologies in order to locally product engineer T cell SCG101. SCG101 clinical trials are currently being conducted at the National University Hospital (NUH) and the National Cancer Centre Singapore (NCCS). The clinical trials are also now open for patient recruitment. SCG101 cell therapy clinical trials will also be conducted in other Southeast Asian countries where the incidence of HBV-related HCC is high.

The Future of Cancer Treatment With Cellular Therapy

Cellular therapy is the most promising of medicine transforming how we treat and potentially cure cancer. In Singapore, research, innovation and enterprise are cornerstones of Singapore’s national strategy to develop a knowledge-based, innovation-driven economy and society.

As part of the Research, Innovation and Enterprise 2020 plan (RIE 2020), Singapore announced that S$80 million will be invested to develop core capabilities required for cell therapy manufacturing. This includes strategic programmes that address the major gaps in advanced cellular therapies manufacturing. It aims to scale manufacturing, automation, cell therapy product development and new technologies for assessing the efficacy, safety, and quality of cells to meet global regulatory and manufacturing standards. This would in turn position Singapore as a global leader in progressing the manufacturing of advanced cellular therapies for decades to come.

SCG is well placed in Singapore, to be the leading biotech company in developing cell therapy focusing on Asia-dominated diseases as it continues to partner with local research institutions to push for an eventual cure for cancer. While SCG already has multiple collaborations with local organisations like A*STAR, HSA-CTF, NUHS, and NCCS, the team is still looking to secure more collaborations for the sharing of knowledge and to accelerate clinical trials.

Cellular therapy could possibly be the future of solid cancer treatments and can potentially open doors to more advanced treatments in the near future. As Singapore’s leading biotechnology company, SCG is determined to advance novel immunotherapies for infections and their associated cancers for a cancer-free future.

References

  1. Gan, E. (2021, August 28). To fight lymphoma, cancer patient first in Singapore to have T-cells genetically modified outside clinical trials. TODAY. Retrieved from https://www.todayonline.com/singapore/fight-lymphoma-cancer-patient-first-singapore-have-t-cells-genetically-modified-outside
  2. Phacilitate. (2020, January 2). Singapore’s Cell Therapy Advanced Manufacturing Programme (STAMP). Phacilitate. Retrieved from https://www.phacilitate.com/singapores-cell-therapy-advanced-manufacturing-programme-stamp/
About the Author

Christy Ma is the Chief Strategy Officer and is a member of the Board of Directors of SCG. Christy is specialised in oncology and immunotherapy drug development.

Before joining SCG, Christy served in various positions in Clinical Operations and Pharmacovigilance at Genentech, BioMarin and FivePrime Therapeutic, with participation in the development of Talzenna® (talazoparib), Cabiralizumab in combination with Opdivo® (nivolumab), Herceptin® (trastuzumab) and Avastin® (bevacizumab).

Christy received a B.S. degree in Chemical Biology from the University of California, Berkeley and her M.S. in Medical Product Development Management from San Jose State University .

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