Traditional cancer treatment methods often lead to significant side effects, which can result in poor quality of life for patients. Therefore, over the past decade, pharmaceutical companies have gradually shifted their development goals toward "specific" and "precise" approaches. Monoclonal antibodies, small molecule drugs, and other targeted therapies have emerged one after another. With the rapid advancement of genetic engineering technology, the latest weapon in the fight against cancer, known as cell therapy, has also come into existence.

In Australia, a 37-year-old male patient with refractory diffuse large B-cell lymphoma (DLBCL) underwent seven treatment courses, including stem cell transplantation, without any improvement in his condition. Ultimately, he achieved complete remission after undergoing cell therapy. Many individuals like him experienced a rebirth through cell therapy, and these clinical cases highlight the limitless potential of cell therapy in the field of cancer.

With the development of new medical technologies, pharmaceutical companies around the world have progressed from molecular drugs to immune cell therapy techniques. Stephen Opat, a clinical hematologist at the Monash Medical Centre and President of the Hematology Society of Australia and New Zealand, along with Alex Huang, Vice President and Head of Cell Therapy at BeiGene, have shared their insights on the subject, discussing the trends and obstacles encountered in advancing cell therapy.

Cell therapy is engineered to target cancer cells with great precision

The principle of cell therapy involves extracting a patient’s immune cells from their own body and cultivating, inducing, and activating the cells in vitro. These cells are then genetically engineered to express specific receptors that can recognize particular antigens in cancer cells. After these modified and enhanced immune cells are reintroduced into the patient’s blood, they can precisely target and attack cancer cells. Moreover, they assist in activating the patient’s immune system to achieve the goal of eliminating cancer cells.

“Just like you take the cells to go to boot camp, make them stronger exactly that.”

Professor Opat explains that the concept of cell therapy can be traced back to 1956 when the medical community first used bone marrow transplantation to treat cancer. Scientists at the time realized that bone marrow transplantation was, in essence, a way to replenish the patient’s immune cells. In 1993, the idea of “engineering immune cells to combat cancer” combined with the development of genetic engineering technology led to the emergence of the first cell therapy product. This cell therapy product was finally introduced in clinical practice in 2009 and led to the complete remission of blood cancer through cell therapy. Since then, the development of cell therapy has progressed rapidly, bringing hope to patients around the world.

The current state and challenges of cell therapy development

Chimeric antigen receptor T-cell therapy, commonly known as CAR-T therapy, is a cutting-edge cancer treatment that involves extracting T cells from a patient's body and modifying them to produce chimeric antigen receptors that can recognize and attach to the antigen present in cancer cells. These modified T cells are then infused back into the patient's body where they work to detect and destroy cancer cells that have the antigen. CAR-T therapy is widely regarded as one of the most promising cell therapy technologies and is currently the subject of intense research being performed by leading pharmaceutical companies.

It is important to understand that the currently approved CAR-T therapies fall under the category of "autologous" cell therapies. The benefit of using a patient's cells is to decrease the risk of immune rejection. However, some cancer patients have weakened immune systems due to previous treatments, which can lead to less stable "source material". The reduced stability of patient’s cells can make the cell modification process more difficult and complex and can impact the effectiveness of chimeric antigen receptor T-cell therapy.

Professor Opat highlighted that many current cell therapies require the transportation of the patient's immune cells to facilities overseas. Moreover, the genetic modification process can take several weeks, which makes it a time-consuming and expensive procedure. The high cost, variations, and prolonged manufacturing process may therefore limit the widespread application of cell therapy.

Exploring new avenues through allogeneic resources

In the field of cell therapy, overcoming the aforementioned challenges brought forth by autologous cell therapy is of the utmost urgency. One promising solution is found in "allogeneic cell therapy" techniques, which involve sourcing immune cells from healthy donors rather than from patients. Allogenic cell therapy could result in a more consistent quality of modified immune cells, making the treatment more consistent and readily available. This approach may become a central focus in the field, as it has the potential to standardize processes and enable mass production of cell therapy products, which would ultimately reduce both time and financial costs.

Alex Huang highlighted that enhancing the efficacy and durability of cell therapy poses a new challenge for the medical industry. BeiGene, is actively participating in this race with the expertise and successful experience gained from the development of the BTK inhibitor zanubrutinib and the anti-PD-1 drug TEVIMBRA to advance research on cell therapy. They envision a future in which allogeneic cell therapy will become a common treatment option for all cancer patients.

Allogeneic techniques illuminating new horizons for unmet treatment needs

Another issue worth discussing is whether the regulatory framework in various countries will keep pace when allogeneic cell therapies mature in the near future. On this matter, both experts have an optimistic outlook.

“Most people believe that innovation and regulation are two sides of the coin. In fact, new therapeutics require mutual learning between the pharmaceutical industry and regulatory bodies to interact effectively,” said Alex Huang.

Based on his experience in Australia, Professor Opat stated that incorporating health insurance or government funding is the final hurdle for the adoption of new therapies. However, he believes that as clinical efficacy evidence accumulates and production costs are controlled, governments will eventually include it in public health care, allowing more patients in need to access this innovative treatment.

Owing to their confidence in the potential and future development of cell therapies, BeiGene officially entered the field in 2021. During the same year, the company announced a strategic partnership with Shoreline Biosciences, a U.S. biotechnology company with a long history of researching natural killer cells. Combining a patient-centered approach and their experience in developing antitumor drugs, BeiGene is dedicated to the development of allogeneic cell therapies.

Professor Opat and Alex Huang share a vision of accelerating the development of innovative cell therapy drugs to bring them closer to cancer patients worldwide. They anticipate that through the development of allogeneic cell therapy techniques, in the future, when cancer patients are in critical condition, they will be able to access high-quality and affordable treatment as readily as picking up medication from a pharmacy. Their goal is to make cell therapy accessible worldwide, addressing the unmet needs of countless cancer patients in the realm of treatment.