Année : 2025

New York Gov. Kathy Hochul and leaders from The Roswell Park Comprehensive Cancer Center came together on Monday to celebrate the opening of the newly expanded Roswell Park Good Manufacturing Engineering and Cell Manufacturing Facility (GMP). This significant undertaking expands Roswell Park’s GMP facility to 11,000 square feet, including 20 clean rooms across two buildings and an entire floor within the Roswell Park Cancer Cell Center. Now the largest academic GMP facility in the state of New York, this milestone marks a transformative step for cancer research and treatment.

The expansion provides cutting-edge cell therapy equipment, manufacturing capabilities and comprehensive quality control, providing a complete spectrum of resources spanning pre-clinical research, clinical manufacturing, clinical trials and implementation. Top specialists in all aspects of cell and gene therapy will lead the work in and around this innovation hub — including Roswell Park team members who helped develop three of the six CAR T-cell therapies now approved by the FDA for treatment of cancer.

“This state-of-the-art facility gives Roswell Park the unique ability to manufacture customized therapies using patients’ own cells right here on site,” said Candace S. Johnson, PhD, President and CEO of the Roswell Park Comprehensive Cancer Center. “Not only will this give our own world-class physicians and scientists the tools and resources needed to advance cancer care, but it also allows us to partner with research organizations and pharmaceutical companies to foster new products and developments.”

The design of the multi-purpose facility will help grow groundbreaking CAR T-cell therapies and also support smaller biotech companies, helping advance therapies that may otherwise be stalled by funding or production constraints. This will ensure the most promising treatments can reach cancer patients faster.

“Our experts are committed to guiding these groundbreaking developments through every stage of the process, ensuring quality, efficiency, and compliance, while focusing on the ultimate goal – patient care and treatment,” said Yeong “Christopher” Choi, PhD, MBA, Technical Director of the Roswell Park’s GMP Facility. “The meticulously planned infrastructure is designed to expedite access to the most promising immunotherapy treatments and is poised to become the largest academic GMP facility in New York State, with insights from the globally acclaimed cell therapy experts at Roswell Park.”

Roswell Park’s Renier Brentjens, MD, PhD, is one of the pioneers of CAR T-cell therapy and has built a team of leading scientists, engineers and oncologists dedicated to advancing these treatments, improving their safety and efficacy and making them more widely available. Five CAR T clinical trials are slated to begin in 2025, utilizing the facility expansion to create these customized treatments.

“These therapies hold remarkable potential to save lives,” said Brentjens, Deputy Director and Chair of Medicine for the Roswell Park Comprehensive Cancer Center. “The GMP Facility allows us to truly blaze the trail to take these from bench to bedside and get them to the patients who need them as quickly as possible.”

To learn more about the unique resources available at the only National Cancer Institute-designated comprehensive cancer center in Upstate New York, as well as the new technology within the Roswell Park GMP Engineering & Cell Manufacturing Facility (GEM), visit roswellpark.org/gmp.

From the world’s first chemotherapy research to the PSA prostate cancer biomarker, Roswell Park Comprehensive Cancer Center generates innovations that shape how cancer is detected, treated and prevented worldwide. Driven to eliminate cancer’s grip on humanity, the Roswell Park team of 4,000 makes compassionate, patient-centered cancer care and services accessible across New York State and beyond. Founded in 1898, Roswell Park was among the first three cancer centers nationwide to become a National Cancer Institute-designated comprehensive cancer center and is the only one to hold this designation in Upstate New York. To learn more about Roswell Park Comprehensive Cancer Center and the Roswell Park Care Network, visit www.roswellpark.org, call 1-800-ROSWELL (1-800-767-9355) or email ASKRoswell@RoswellPark.org.

Media Contact

Annie Deck-Miller, Director of Public Relations
716-845-8593; annie.deck-miller@roswellpark.org

Researchers publishing in Physical Review X have discovered compounds that can double the efficiency of the sirtuin SIRT3 in processing NAD+.

Looking for a new way to boost enzymes

The researchers begin their paper by noting that most drugs administered to people are geared towards inhibition of particular enzymes in order to treat a disease. In this case, however, the goal is the opposite: to boost the function of an enzyme, thereby boosting a healthy phenotype rather than battling back a diseased one.

Sirtuins are enzymes that have been heavily investigated in the context of aging. They rely on NAD+ to function, and these researchers describe them as being critical regulators of cellular pathways relating to aging [1]. Upregulating sirtuins has been found in considerable previous work to extend lifespan in mammals [2]. However, most methods of using drugs to boost sirtuins has relied on allosteric activation, a chemical process that relies on an existing substrate that might be limited in quantity [3].

Of course, as sirtuins rely on NAD+, there has been much work on directly influencing that instead. These researchers note two problems with that approach: as it is a common aspect of metabolism, boosting NAD+ across the board may result in broad side effects [4] and converting it into NADH relies on delivering it into cells that have functioning internal machinery [5], which, in the context of aging, is far from guaranteed.

Therefore, these researchers seek to allow sirtuins to do more with less: to continue to function adequately even when NAD+ is diminished. This, the researchers describe, is a trickier thing to do; while allosteric activators fundamentally rely on existing, evolved mechanisms, attempting to modulate these enzymes is similar to designing new enzymes outright.

Also, they needed a compound that works all the time: a steady-state activator. Previous work has created compounds that inhibit, rather than activate, sirtuins most of the time [6], only performing their desired function under specific conditions.

SIRT3 was chosen as the target for two reasons. The first is that it is known to have beneficial effects on mitochondria [7], and previous work has found that the benefits of NAD+ against mitochondrial dysfunction are due to SIRT3 [8]. The second is that natural mutations in the SIRT3 gene are connected to longevity [9].

Needle in a haystack

Using an advanced algorithm, the researchers searched a library of 1.2 million compounds by beginning with Honokiol, a compound that only activates SIRT3 under certain conditions. The researchers were able to find compounds that do steady state and non-steady state activation, with which they refined their experiments further with a close and detailed examination of the specific biochemistry involved, looking for compounds that have strong bonds to certain amino acids on the SIRT3 protein.

This initial work, however, was all done on computers. To verify their findings in the real world, the authors administered their compounds to real SIRT3 in a substrate. While a lot of this type of work uses fluorescent labeling, the authors eschewed that approach as it may have affected the results. One particularly strong compound, number 5689785, was identified as being a plausible drug after this screening process.

The researchers tested their new candidate against a control group, honokiol, and the well-known NAD+ precursor NMN. In nearly all cases, 5689785 performed favorably against these alternatives. Administering nicotinamide (NAM) to cells inhibits NAD+ enzymatic activity, but 5689785 was able to restore it in a way that honokiol could not.

Next steps

This is not a drug yet; it has not been formulated in a way that is consumable by living organisms, and so there were no animal studies done. What the researchers have is an initial compound with which to continue the process of drug development. Their goal was to prove that it is indeed possible to directly enhance the activity of sirtuins without relying on substrate-based methods. If this approach sees success in animal models, it could pave the way for drugs that, due to SIRT3’s mitochondrial effects, fight multiple aspects of aging.

Literature

[1] Kaeberlein, M., McVey, M., & Guarente, L. (1999). The SIR2/3/4 complex and SIR2 alone promote longevity in Saccharomyces cerevisiae by two different mechanisms. Genes & development, 13(19), 2570-2580.

[2] Roichman, A., Elhanati, S., Aon, M. A., Abramovich, I., Di Francesco, A., Shahar, Y., … & Cohen, H. Y. (2021). Restoration of energy homeostasis by SIRT6 extends healthy lifespan. Nature communications, 12(1), 3208.

[3] Sinclair, D. A., & Guarente, L. (2014). Small-molecule allosteric activators of sirtuins. Annual review of pharmacology and toxicology, 54(1), 363-380.

[4] Yang, T., & Sauve, A. A. (2006). NAD metabolism and sirtuins: metabolic regulation of protein deacetylation in stress and toxicity. The AAPS journal, 8, E632-E643.

[5] Hu, Q., Wu, D., Walker, M., Wang, P., Tian, R., & Wang, W. (2021). Genetically encoded biosensors for evaluating NAD+/NADH ratio in cytosolic and mitochondrial compartments. Cell reports methods, 1(7).

[6] Reverdy, C., Gitton, G., Guan, X., Adhya, I., Dumpati, R. K., Roy, S., … & Chakrabarti, R. (2022). Discovery of novel compounds as potent activators of Sirt3. Bioorganic & medicinal chemistry, 73, 116999.

[7] Van de Ven, R. A., Santos, D., & Haigis, M. C. (2017). Mitochondrial sirtuins and molecular mechanisms of aging. Trends in molecular medicine, 23(4), 320-331.

[8] Cantó, C., Houtkooper, R. H., Pirinen, E., Youn, D. Y., Oosterveer, M. H., Cen, Y., … & Auwerx, J. (2012). The NAD+ precursor nicotinamide riboside enhances oxidative metabolism and protects against high-fat diet-induced obesity. Cell metabolism, 15(6), 838-847.

[9] Bellizzi, D., Rose, G., Cavalcante, P., Covello, G., Dato, S., De Rango, F., … & De Benedictis, G. (2005). A novel VNTR enhancer within the SIRT3 gene, a human homologue of SIR2, is associated with survival at oldest ages. Genomics, 85(2), 258-263.

Founders Longevity Forum Singapore, hosted in collaboration with the National University of Singapore (NUS) Academy for Healthy Longevity, Yong Loo Lin School of Medicine, and Longevity.Technology is set to host a pivotal two-day event on 27-28 February 2025, in Singapore. This forum aims to advance knowledge and foster growth in the rapidly evolving field of longevity, with a special emphasis on the Asia-Pacific (APAC) region.

Building upon the immense success of the Unlock Healthy Longevity Conference of the NUS Academy for Healthy Longevity and the inaugural Founders Longevity Forum held in London in 2024, the Singapore event will convene global leaders, clinicians, academics, and investors to explore advancements in extending health span and addressing the challenges of ageing. The forum will feature a dynamic roster of speakers, including experts in epigenetics, AI, cryomedicine, and preventative healthcare.

The event is structured to allow attendees to engage with content relevant to their specific interests through two distinct tracks: Precision Geromedicine and Longevity Investment. Sessions will cover a broad spectrum of topics, from biomarkers of ageing and consumer diagnostics to investment opportunities in the wellness and gym sectors embracing longevity.

Prof Andrea Maier, Oon Chiew Seng Professor in Medicine, NUS highlights the importance of the multidisciplinary approach of the conference, saying: “Precision Geromedicine is an emerging field and increasingly implemented into clinical practice to optimise the health of ageing individuals. Gerodiagnostics to measure the biological age and gerotherapeutics to lower the biological age are needed to build clinically meaningful and cost-effective services. This conference is stimulating the interaction of stakeholders to build this hugely important ecosystem.”

Carolyn Dawson, CEO of Founders Forum Group, said: “We are thrilled to bring Founders Longevity Forum to Singapore in collaboration with the National University of Singapore (NUS) Academy for Healthy Longevity, Yong Loo Lin School of Medicine and Longevity.Technology. This event is a testament to the rapid advancements and investment opportunities emerging in the Asia-Pacific longevity sector. By uniting global experts, investors, and innovators, we aim to catalyse breakthroughs in healthspan and ageing science, empowering the next generation of founders and leaders to shape a healthier and more sustainable future for all.”

Phil Newman, Founder and CEO of Longevity.Technology, emphasised the significance of the event, stating: “Founders Longevity Forum Singapore represents a unique convergence of scientific innovation, investment potential, and consumer engagement in the longevity sector. With the APAC region experiencing rapid growth in longevity marketing, this forum offers unparalleled networking opportunities and insights into the future of healthy ageing.”

Ticketing for the event is live, and attendees are encouraged to register promptly to secure their participation.

https://founderslongevity.co/sg/

About Founders Longevity Forum

Founded by Founders Forum Group and Longevity.Technology, Founders Longevity Forum is a premier event series dedicated to advancing the field of longevity science and technology. In collaboration with leading academic institutions and industry partners, the forum provides a platform for thought leaders, innovators, and investors to drive progress in extending healthspan and addressing the challenges of ageing.

About Founders Forum Group

Founders Forum Group is a global community and group of businesses supporting entrepreneurs at every stage of their journeys.

Its forums unite the world’s most influential founders, investors, corporate and government leaders to tackle era-defining questions in iconic locations across the globe.

Since 2019, Founders Forum has partnered with Informa Tech to celebrate the strength and diversity of UK tech through London Tech Week.

Fuelled by the connections and ideas forged at the group’s flagship events, FF Group businesses support the needs of today’s founders via services (Founders Keepers, Founders Law, Founders Makers, Miroma Founders Network, Founders HR, Founders Comms, Founders Health), education (01 Founders), investment (Founders Factory, firstminute capital), networking (Grip, INDI), philanthropy (Founders Pledge, The Centre for Entrepreneurs), and content (Founders Insights). In 2021, the group sold its innovation strategy consulting firm, Founders Intelligence, to global consultancy, Accenture.

In 2023, FF Group acquired Tech Nation, the UK’s leading growth platform for tech scaleups. Founders Forum Group continues the previously government-funded Tech Nation programmes centred around early-stage and diverse founders, as well as data-driven research into the UK’s tech ecosystem.

For more information, contact:

Sean Lau

Head of Asia, Founders Forum Group

Sean@ff.co