Immunotherapy represents a new paradigm in cancer care. It’s really an entirely new mechanism for treating cancer. We’re not targeting the tumor cells; instead, we’re targeting the immune system.
I encourage patients to talk with their physicians about innovative treatment options and consider participating in clinical trials so we can move the field forward. Together, we can unlock the promise of immunotherapy.
Lynch Syndrome, a genetic condition affecting around 1 million Americans annually, increases a person’s risk of developing colorectal cancer (CRC) to 20% – 80%.
As a result, Lynch Syndrome patients must complete yearly preventive screenings. However, developing a Lynch Syndrome vaccine could change the narrative for patients, reducing screenings and – more importantly – lowering risks for Lynch Syndrome-related cancers.
“The advances in vaccine technologies, such as Lynch Syndrome, is a promising field of research that has the potential to reduce the risk of developing cancer, thereby preventing disease and modifying surveillance regimens for high-risk patients,” said David Fenstermacher, Senior Director of Research & Medical Affairs at the Colorectal Cancer Alliance.
Safe and effective cancer prevention strategies are critically needed to improve the life quality and longevity of LS and other Hereditary Cancer Syndrome carriers.The era of precision oncology driven by recent technological advances in tumor molecular profiling and a better understanding of genetic risk factors has transformed cancer prevention approaches for at-risk individuals, including LS carriers.
Here, they discuss recent advances in precision cancer immunoprevention approaches, emerging enabling technologies, research gaps, and implementation barriers toward clinical translation of risk-tailored prevention strategies for LS carriers.
The success of FSP neoantigen(mutation)-based cancer vaccines for LS cancer prevention will hopefully demonstrate the potential marketability of cancer preventive vaccines in the next decade, which will bring an increasing interest from the private sector and can lead to the partnership opportunities between academia, government, and industry for the betterment of quality of life for LS and other high-risk populations.
The leaders of those trials and other experts stressed that much more research is needed before this treatment approach becomes part of everyday cancer care. But they agreed that the findings so far are highly encouraging.
The most recent results come from a 35-patient clinical trial conducted at MD Anderson Cancer Center. Most patients in the trial had locally advanced colorectal cancer. Perhaps most important, however, was that all participants’ tumors had specific genetic changes—known as MSI-high or dMMR—that make them particularly good candidates for immunotherapy.
Researchers have recruited the first vaccine candidates to one of two new prevention trials that seek to immunize high-risk individuals against Lynch syndrome, the most common cause of hereditary colorectal cancer. Individuals who inherit the condition have an estimated lifetime risk as high as 80% for developing one of these malignancies, as well as an above-average risk for cancers arising in other organs, often at an early age, and regardless of race or gender.
The Nous-209 vaccine—named partially for the number of neoantigens or “new” antigens it contains, and in part for the Switzerland-based company (Nouscom) that developed it—employs what investigators call “a brute force” approach. The vaccine contains 209 bits and pieces of cancer-specific neoantigens expressed only in premalignant or malignant tissues of individuals with Lynch syndrome thatresearchers hope will stimulate a robust immune-system attack that stops cancer progression at its origin.
In comparison, the Tri-Ad5 vaccines, developed through the National Cancer Institute’s (NCI’s) intramural program, rely on three tumor-associated antigens that are overexpressed in cancer cells, but are also found to a lesser degree in healthy tissues. Because early studies suggested that the approach with only the MUC-1 antigen showed promise, investigators added two other antigens (CEA and brachyury) in the Tri-Ad5 vaccines, which will be combined with an Interleukin-15 (IL-15) “superagonist,” a vaccine stimulant, to increase the vaccine’s potential for destroying premalignant lesions or early tumors.
“Right now, we are focused on helping high-risk populations, and they, in turn, are teaching us how to develop better cancer preventive vaccines for the future.”
“There is much to be optimistic about right now for those with Lynch. Many medical discoveries and advances have been made within the past decade. Aspirin is used as a chemoprevention, immunotherapy may put various Lynch syndrome-related cancer in remission, and AI is improving screening measures, specifically for colonoscopies. What excites me the most is the Lynch vaccine in clinical trials now. The Lynch landscape has changed since my diagnosis 12 years ago.”