The flight of Sahin over peak BNT116
Extreme fatigue, unexplained weight loss, pain, skin changes, fever and night sweats, and headaches—many of us have experienced some of these symptoms at various points in our lives. However, the simultaneous occurrence of most or all of these symptoms is alarming and should not be overlooked because it may signify cancer. It is terrifying to even imagine that, one day, our body cells might uncontrollably start multiplying with no reason. What is the solution?
MSTF media reports
“The biggest challenge for cancer treatment is that every patient has a different type of cancer. Even within one patient, there are billions of cancer cells, each differing from the other. Current cancer treatment methods often overlook this challenge which is why only 20 to 30 percent of cancer patients typically respond to treatment,” explains Ugur Sahin, a laureate of the Mustafa(pbuh) Prize in the field of Life and Medical Science and Technology. He is also the driving force behind the cancer vaccine "BNT116" which has recently been put to clinical trials.
Cancer is a complicated disease influenced by two types of gene mutations: primary and secondary. Primary mutations initiate cancer while secondary mutations arise as a result of uncontrolled cell proliferation, exacerbating the disease. Secondary mutations add traits to cancer cells such as viability, ability to migrate, and resistance to the immune system. Each of these genes can be a therapeutic target for cancer. Moreover, cancer cells produce proteins that cannot normally be found in normal cells, yet the immune system cannot detect them as malignant foreign molecules since they use mechanisms to bypass it. No two cancer patients share the same genetic mutations in their cancer cells. As a result, each patient's treatment has to be personalized.
The only system of the human body that can be modulated is the immune system. Therefore, it has to be stimulated against cancer cells and attack them. “My research is focused on immunotherapy. We are developing treatments such as vaccines and antibodies to strengthen the patient's immune response to cancer cells,” Sahin states. He is the CEO and co-founder of BioNTech, a company specializing in patient-specific vaccines for cancer and contagious diseases. Founded in 2008, BioNTech is a pioneer in manufacturing mRNA vaccines.
mRNA, or messenger RNA, is a vital molecule capable of producing antibodies, antigens, cytokines, etc., and its half-life can be adjusted. These types of vaccines belong to the new category of RNA therapy and unlike gene therapy, they do not carry the risk of being integrated into the DNA of the target cell. Because of its rapid production, mRNA can be used for many therapeutic purposes.
Sahin was awarded the 2019 Mustafa(pbuh) Prize for his work on “Development and Clinical Testing of mRNA-based Cancer Vaccines that are tailored to the Mutation Profile of a Cancer Patient.” During the COVID-19 Pandemic, Sahin leveraged the same technology to develop the BNT162b2 Coronavirus vaccine in less than a year. A joint product of BioNTech and Pfizer, the vaccine received FDA approval in 2020. With an efficacy of more than 95%, it played a significant role in curbing COVID-19 across the world. BioNTech’s mission did not end with creating a coronavirus vaccine. After two decades of research on mRNA, Ugur Sahin is now closer than ever to revolutionizing cancer treatment. The BNT116 vaccine for lung cancer and BNT111 for melanoma are evidence of this progress.
Recently, the clinical trials for BNT116, BioNTech’s latest product, has begun. This vaccine is developed to treat the most common type of lung cancer, non-small cell lung cancer (NSCLC). According to annual research conducted in the United States, lung cancer is the third most common cancer. Of this amount, 80% of patients have non-small cell lung cancer (NSCLC) and the rest have small cell lung cancer (SCLC). Tragically, lung cancer claims 1.8 million lives each year.
Cancer Cells’ Achilles Heel
mRNA cancer vaccines have shown that cancer cells can indeed be trapped. By using the specific proteins unique to cancer cells we can signal the immune system to recognize tumors. This is achieved by introducing these antigenic proteins to the immune system as markers of malignancy. Through a complex molecular process, known as RNA Therapy, Sahin delivers these cancer cell antigens to the immune system. In this process, abnormal proteins are converted into RNA which then enter the body and the immune system cells through certain processes. A group of cells of the immune system called dendritic cells (DCs) act as antigen-presenters, playing a vital role in presenting harmful antigens to T-cells, the soldiers of the body, thereby inducing an immune response.
Sahin has provided solutions to transport mRNA into dendritic cells more effectively. One such solution involves using a type of nanoparticle that delivers antigen-encoding mRNA to dendritic cells and strengthens the immune response of T-cells. Then, these coding RNAs must be converted into the antigen that signals the presence of cancer cells. So, they are expressed by ribosome, intracellular organelles responsible for making proteins. Ultimately, these antigens reach the body's T-cells which then locate cancerous tumors and attack them. The immune system finds and destroys cancer cells more easily and more proficiently.
Sahin's team uses different platforms to develop their vaccines. BNT116 is built on the FixVac (Fixed Vaccines) platform, which uses the abovementioned mechanism of cancer cell antigen presentation. BioNTech designs mRNA cancer vaccines on the two platforms iNeST and FixVac, each of which has its own characteristics. To increase the efficiency of FixVac vaccines, the company has used uridine mRNA (uRNA), which improves their immunostimulatory effect.
Throughout their research, Sahin and his team have encountered many challenges in optimizing mRNA cancer vaccines; therefore they have taken many things into account: The vaccine must be capable of stimulating billions of immune cells because small tumors are made up of billions of cancer cells. They worked on the discovery and engineering of the components of the mRNA molecule—such as the cap, a poly(A) tail and its untranslated regions—to increase its intracellular stability and translation efficiency. By combining these improved elements, these researchers were able to increase protein expression by more than 1000 times. They were also able to increase the effectiveness of the vaccine by discovering a mechanism that led to the selective absorption of mRNA into dendritic cells, particularly dendritic cells in lymphatic tissues. Dendritic cells have the ability to induce a primary immune response in inactive or quiescent T lymphocytes, thereby enhancing the immune response. Sahin’s team also designed a method for dendritic cells to present antigens more effectively to immune cells to produce a stronger immune response, using antigen pairing or major histocompatibility complex (MHC-I).
The German company’s clinical trial of the BNT116 vaccine started in August 2024, involving about 130 participants across 34 research centers in seven countries, including America, Germany, Bulgaria, Poland, Spain and Turkey. Patients in this study are at different stages of cancer. Mr. Racz, 67, from London, is the first recipient of the vaccine. Diagnosed with lung cancer in May, he has been receiving chemotherapy and radiation therapy since then. Racz received his initial dose of the vaccine through six consecutive injections with five-minute intervals. He will continue with weekly vaccinations for six consecutive weeks, followed by vaccinations every three weeks for a total duration of 54 weeks.
This trial aims to determine the safety and appropriate dosage of the drug. The volunteers in this trial are patients currently being treated with only one drug called cemiplimab. The results will reveal how safe and tolerable the vaccine will be when administrated alongside the drug. Furthermore, the study will compare the outcomes of patients receiving both the cemiplimab drug and the vaccine against those receiving only the cemiplimab drug without the vaccine. If the vaccine successfully passes the clinical trial, it will be close to receiving the approval of the United States Food and Drug Administration (FDA) and subsequently become available in global markets.
Creativity is the key!
There was a time when the idea of a cancer vaccine seemed so far-fetched that it was rarely discussed in scientific circles. Back then, it felt like nothing more than a dream. What sets Ugur Sahin apart from others is his willingness to break away from traditional approaches and develop innovative solutions to complex problems. It doesn't matter if one is a researcher, doctor or comes from any other field. What truly matters is the commitment to success and tangible results. With this mindset, it doesn't matter how long the journey takes and how many obstacles one faces. Ugur Sahin is a role model for all who dedicate their intellect and passion to improving life, giving hope to those who wish to live longer, experience more and laugh more heartily. This scientist whose surname means "falcon" in his native language, remains one of the leading scientists in the fight against cancer.
