COLUMBUS, OHIO – Scientists with The Ohio State University Comprehensive Cancer Center – Arthur G. James Cancer Hospital and Richard J. Solove Research Institute (OSUCCC – James) developed and preclinically validated a B cell-based immunotherapy that activates the immune system to fight cancers linked to high-risk human papillomavirus (HPV) infection. Through the Drug Development Institute at the OSUCCC – James, the university has partnered with Activate Biosciences as an industrial development partner to move this novel immunotherapy into clinical testing. First-in-human clinical testing is expected to start at the OSUCCC – James in 18 to 24 months. Nearly all – an estimated 99.7% – of cervical cancers are linked to high-risk HPV infections. Rates of HPV-related head and neck cancers continue to rise, with data indicating it will become one of the most common forms of cancer in adults between the ages 45 to 65 and among the top three cancers affecting middle-aged men in the United States by 2045. “This approach to immune system activation is novel and designed to boost an individual’s ability to combat HPV-associated malignancies” said Thomas Cherpes, MD, DVM. “Studies in preclinical models of HPV-associated tumors show that this new technology primes the individual’s own T cell-mediated immunity and then effectively identifies and eradicates cancer cells.” How new immunotherapy technology overcomes existing challenges This new and proprietary B cell-based immunotherapy was discovered in the lab of Cherpes and Rodolfo Vicetti Miguel, MD, translational scientists in the OSUCCC – James Translational Therapeutics Research Program and The Ohio State University College of Medicine Department of Otolaryngology. Researchers say this new platform technology overcomes challenges with efficient antigen delivery and immune stimulation that have limited the effectiveness of prior attempts to activate the immune system against cancer. “Triggering the immune system to recognize and attack cancer cells is challenging. Our approach is built upon current principles of immune cell activation and limitations of prior attempts to use a cell-based platform to combat cancer. To date, our studies in preclinical models show this new technology enhances the individual’s ability to eradicate cancer. Because it generates long-lived immune memory cells specific for a particular cancer, it also has the potential to lower the risk that cancer returns,” said Vicetti Miguel. To create this immunotherapy, a patient’s B cells (immune cells) are collected, activated, and expanded 50- to 100-fold in a lab and readministered back to the patient. Unlike chimeric antigen receptor (CAR) T-cell immunotherapy, the B cells do not require genetic engineering, making them quicker to manufacture and more cost effective. The activated B cells then give the body’s immune system a kickstart to recognize and specifically target cancer cells. Working with the DDI and OSUCCC – James cancer physicians James Rocco, MD, PhD, and David O’Malley, MD, the team conducted preclinical tests to show this immunotherapy was effective in treating preclinical models of HPV-linked cancer. Future clinical trials will start with patients who have head and neck cancer and cervical cancers. “The link between high-risk HPV and cancer continues to increase, spanning beyond head and neck and cervical and other areas targeted by this type of cancer. An immunotherapy to boost the body’s ability to fight these cancers and prevent their recurrence could be a real treatment game changer,” said O’Malley, who serves as gynecologic oncology division chief and is a translational scientist at the OSUCCC – James. High-risk HPV and cancer risk, prevention HPV is a large group of viruses spread through skin-to-skin and oral contact that occurs during sexual activity. The virus spreads easily, and an estimated 98% of the population has been exposed to it. HPV can remain dormant for decades. High-risk strains of the virus have long been linked to increased risk of cervical cancer; however, data from the past decade shows high-risk HPV is also strongly linked to cancers of the head and neck (mouth, base of tongue and throat). In 2006, Merck introduced an HPV vaccine called Gardasil, which is administered in youth between the ages of 9 and 26. The vaccine protects against multiple HPV strains, including the high-risk strains of the virus (HPV 16 and HPV 18) that are linked to cancer, including cervical, vulvar, throat, mouth, penis and anal cancer. There are many other HPV strains that can cause non-cancer conditions such as genital warts. Although it has been available for nearly two decades, lack of awareness about it as a means of cancer prevention later in life has slowed progress in preventing these cancers. The Centers for Disease Control and Prevention (CDC) estimates that timely HPV vaccination could prevent 90% of cervical cancers alone. The National Cancer Institute estimates that as of 2020 just 54.5% of youth between the ages of 13 and 15 were vaccinated. Rocco notes it is important to understand that this new immunotherapy developed at the OSUCCC – James is fundamentally different from preventive HPV vaccines such as Gardasil. “While Gardasil is given before exposure to prevent HPV infection, this new immunotherapy is designed for patients who have developed cancers associated with prior HPV infection. Rather than preventing infection, it works by activating the patient’s immune system to recognize and attack HPV-driven cancer cells, with the goal of improving treatment effectiveness and reducing cancer recurrence risk,” said Rocco, who serves as the Mary E. and John W. Alford Research Chair in Head and Neck Cancer at Ohio State’s College of Medicine and is a scientist with the OSUCCC – James Translational Research Program. To learn more about research and patient care at the OSUCCC – James, visit cancer.osu.edu. ###