Trials Test Vaccines for Prevention or Delay of Cancers Associated with Lynch Syndrome

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 vaccinenamed 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 that researchers 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.

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