Throughout CRI’s history, we have supported a variety of basic research projects aimed at improving our understanding of the principles behind vaccines and strategies to identify the most promising vaccine targets as well as translational and clinical efforts that seek to use these insights in the development of cancer vaccines for patients in the clinic.
In 1959, Lloyd J. Old, M.D., CRI’s founding scientific and medical director, showed that the tuberculosis vaccine Bacillus Calmette-Guérin (BCG) could inhibit tumor growth in mice. Then, in 1980, CRI-funded grantee Alvaro Morales, M.D., of Queen's University (Canada), demonstrated that BCG can prevent bladder cancer recurrence in human patients. The FDA approved the use of BCG for superficial bladder cancer in 1990.
Additionally, CRI has supported over two decades of research on the NY-ESO-1 antigen, a cancer vaccine target. In 2017, CRI grantees Sacha Gnjatic, Ph.D., of the Icahn School of Medicine at Mount Sinai, and Kunle Odunsi, M.D., Ph.D., of the Roswell Park Comprehensive Cancer Center, found that vaccines against NY-ESO-1 were associated with improved survival in patients with aggressive ovarian cancer. This was based on work throughout the 2000s from CRI-funded scientists—including Maha Ayyoub, M.D., Ph.D., Nina Bhardwaj, M.D., Ph.D., Dirk Jaeger, M.D., Elke Jaeger, M.D., Alexander Knuth, M.D., Lloyd J. Old, M.D., Gerd Ritter, Ph.D., and Danila Valmori, Ph.D.—that advanced our understanding and development of NY-ESO-1-targeting vaccines in a variety of cancers.
Other important contributions made by CRI scientists in the area of cancer vaccines include:
- In 2001, CRI grantee Ian H. Frazer, M.D., of the University of Queensland, made important breakthroughs regarding human papilloma virus (HPV)-targeting vaccines that paved the way for the development of the first preventive cervical cancer vaccine, Gardasil®.
- In 2009, CRI grantees Sjoerd van der Burg, Ph.D., and Cornelis Melief, M.D., Ph.D., both of the Leiden University Medical Center, found that a vaccine composed of human papilloma virus (HPV) long peptides could produce durable complete responses in some women with HPV-16+ pre-cancer of the vulva.
- In 2012, CRI predoctoral fellow Matthew Vesely, Ph.D., and CRI grantee Robert Schreiber, Ph.D., highlighted how next generation sequencing could be used to characterize tumor neoantigens for the development of vaccines.
Currently, CRI is funding several grantees whose research involves cancer vaccines, including deciphering decipher the rules that govern the intracellular processing of (neo-)antigens and their presentation on the surface of cells, exploring the use of nanoparticles to deliver “intel” to the immune system about what cancer “looks like,” and analyzing patients whose immune systems naturally eliminated hepatitis C virus (HCV) infections. CRI is also providing funding support for a phase 1/2 clinical trial (NCT03164772) combining two checkpoint inhibitors with a cancer vaccine in patients with advanced lung cancer.