Anca Apavaloaei, PhD, CRI Immuno-Informatics Fellow

About 50% of the human genome consists of repetitive sequences, called retrotransposons, derived from ancient viruses that integrated into our germline DNA and replicated over millions of years. Due to accumulated mutations, most retrotransposons have lost their capacity to replicate. However, the LINE-1 retrotransposon maintains replication capacity at around 100 out of its half a million genomic copies. Normal cells employ mechanisms to suppress LINE-1 expression and replication, but these mechanisms are disrupted in cancer. Whereas LINE-1 activity can promote tumor development, it can also serve as a target for therapies.

In this project, Dr. Aprovaloaei will evaluate whether LINE-1 expression in cancer cells generates tumor antigens that can be seen as foreign by the immune system. If she is able to identify LINE-1-derived tumor antigens with immunogenic potential, this would allow for the development of anti-cancer vaccines using synthetic analogs of these antigens to train the immune system to effectively recognize and attack cancer cells expressing LINE-1 antigens. A vaccine targeting LINE-1 antigens would confer unique off-the-shelf treatment opportunities for multiple cancer types because LINE-1 is expressed by many cancers, regardless of their mutational burden. Furthermore, Dr. Aprovaloaei also plans to test if LINE-1 vaccines boost the efficacy of available immune-based therapies, using mouse tumor models. Overall, Dr. Aprovaloaei’s study will start with the analysis of gastroesophageal cancer samples which show the highest expression of LINE-1 across cancers and later expand to other cancers, including melanoma and lung cancer. If successful, this research will lead to novel immune-based therapies for many patients.

Projects and Grants

Identification of LINE-1-derived antigens for development of off-the-shelf anti-cancer vaccines

Weill Cornell Medicine | All Cancers | 2025 | Taha Merghoub, PhD, and Benjamin Greenbaum, PhD