Clinical trials are soon to be underway to examine the effectiveness of vaccines meant to prevent or delay cancer in high-risk individuals. Led by an MD Anderson oncologist and geneticist, Eduardo Vilar-Sanchez, the clinical trial will include patients with Lynch syndrome.
A heritable genetic disorder, Lynch syndrome involves a mutation to a DNA repair gene that leads to genetic errors that put patients with this syndrome at a high risk for cancer – a 70% lifetime risk for it. Lynch syndrome is estimated to affect 1.1 million people in the US.
"There is a lot of anxiety in this patient population. It is a big psychological burden," states Vilar-Sanchez.
Patients with Lynch syndrome can develop cancer early and need frequent, early screenings for cancer detection in hopes of early intervention.
Although vaccines already exist to prevent virus-associated cancers, like hepatitis B and liver cancer or human papillomavirus and cervical cancer, this is one of the first clinical tests of vaccines to prevent nonviral cancers.
Cancer vaccines have also been used to treat certain cancers. There is currently only one approved cancer treatment vaccine that's used to treat advanced prostate cancer. It's been shown to extend life by just 4 months. The focus in this clinical trial will be the use of cancer vaccines as a more preventative method.
Based on insight into genetic changes in early cancers, these vaccines will deliver antigens from cancer cells into the body to trigger an immune response meant to attack tumors when they form. The idea is to vaccinate patients with Lynch syndrome while they're still healthy and before their immune system becomes suppressed by tumors or cancer treatments like chemotherapy, so that they mount a better immune response to the vaccine.
One hurdle is choosing which antigens vaccines deliver. If antigens in vaccines are more widely present in areas of the body outside of a tumor, these vaccines could risk initiating autoimmunity. If vaccines don't deliver a broader array of antigens, they may not be very effective at shielding against cancer in conditions where multiple tumors form.
The key may be vaccines that target neoantigens, or those antigens found only on cancer cells. Neoantigens have been detected through tumor genome sequencing. Unfortunately, these neoantigens are usually unique to an individual cancer and aren't known until after cancer forms. But in the case of Lynch syndrome cancers, these neoantigens are more predictable, making preventative cancer vaccines more practical.
The vaccine in this upcoming clinical trial will contain a broad variety of neoantigens to try to tackle the obstacle of different individuals' tumors having different sets of antigens. Investigators are looking to see whether the vaccine stimulates an immune response and has an effect on polyp or tumor formation in 45 patients with Lynch syndrome who have either never had tumors or are in remission after cancer treatment.
Sources: Science