"The immune system is usually capable of detecting and removing the tumor cells. Nevertheless, virtually all cancers— including the most common cancers, from lung, breast, and colon cancers to melanomas and lymphomas — are emerging to combat and overcome such immune surveillance by co-opting and amplifying the natural mechanisms of immune suppression, "says Atul Bedi, M.D., M.B.A., associate professor of otolaryngology-head and neck surgery at the Johns Hopkins University School of Medi.
The major way tumors invade the immune system is through regulatory T cells (Tregs), a subset of immune
"This is particularly challenging because Tregs is not only caused by TGFbeta (transforming growth factor-beta) protein formed by tumor cells but also allows TGFbeta to maintain its own identity and function in the tumor," says Bedi. Tregs also produce cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) which prevents anti-tumor immune cells from functioning.
To address this issue, scientists have invented a new class of immunotherapy drugs called Y-traps. Every Y-trap molecule is an antibody shaped like a Y and fused to a molecular "trap" which traps other molecules in the vicinity, making them useless.
Antibodies to another immune checkpoint protein, PD-1 or its ligand (PD-L1), are at the core of modern cancer immunotherapy. Although they work in some patients, they do not work in the vast majority of patients.
"These first-in-class Y-traps are only the start. We have already discovered a whole family of these multifunctional molecules based on the technology of Y-trap. Because immune dysfunction mechanisms are shared across many
"This technique appears to be a groundbreaking method and an exciting technical achievement to target multiple tumor microenvironment suppression mechanisms," says Robert Ferris, MD, Ph.D., Professor of Oncology and Director of the Hillman Cancer Center at the University of Pittsburgh. Ferris was not related to the report. "I look forward to seeing its introduction to the hospital." Bedi plans to use Y-traps not only for the treatment of advanced metastatic cancers but also as neoadjuvant therapy to create a "vaccine" effect— that is, to give them to patients before surgery to prevent recurrence of the disease.
Other members of the study are Rajani Ravi, Kimberly Noonan, Vui Pham, Piotr Wysocki, Ranee Mehra, Sridhar Nimmagadda, Luigi Marchionni, David Sidransky, Ivan Borrello and Evgeny Izumchenko of Johns Hopkins University, Alex Zhavoronkov, Ivan Ozerov, Eugene Makarov, Artem Artemov of Insilico Medicine, and Rishi Bedi of Stanford University.