Researchers at Oregon Health & Science University (OHSU) shared in May 2024 that their platform for cytomegalovirus-based vaccines has “promise” as a “shield” against cancer. Their paper in Science Advances presents the results of immunising rhesus macaques (RM) with rhesus cytomegalovirus (RhCMV) vectors that were genetically programmed to elicit major histocompatibility complex E (MHC-E)-restricted CD8+ T cells and to expressed established tumour-associated antigens (TAAs). They found that their vaccine established a “long-lasting” defence.
HIV applications
The team began working on the vaccine platform in the early 2000s, with initial research focusing on an HIV T cell vaccine. Early clinical trials established the safety of the platform, and the researchers have since modified the vaccine in search of the “desired immune responses”. Results from these efforts are expected later in the year.
The latest study expands the research to investigate the CMV vaccine platform against cancer. The researchers used genetically modified RhCMV to induce cancer-specific T cells, which “recognise infected cells in a unique manner”. The data indicate that CMV-based vectors can be used to generate MHC-E-restricted CD8+ T cells to “common cancer antigens” and that cancer cells can “present tumour antigens to these T cells via HLA-E”.
“Targeting HLA-E is therefore a new modality for cancer immunotherapy.”
Unconventional T cells
Dr Klaus Früh, professor in OHSU’s Vaccine & Gene Therapy Institute, commented that the team’s research reveals that cytomegalovirus can induce unconventional T cells to cancer antigens; these unconventional T cells can recognise cancer cells.
“The idea is that by throwing a type of T cell against the cancer that the cancer hasn’t seen before, it will have a harder time evading immunity.”
Dr Früh suggests that “eliciting T cells to cancer antigens is not easy” because it goes against what the “immune system has been trained not to do”.
“Overcoming this immunological tolerance is a challenge for all cancer vaccines.”
The platform’s potential is exciting, with lasting protection suggesting that it could prevent cancer reoccurrence.
“If you’ve had a cancer, you are worried the rest of your life that it may come back. So having a vaccine that can elicit cancer-specific T cells that act as an immune shield continuously patrolling your body and that would protect you for the rest of your life, it’s just really exciting.”
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