In findings from Brigham and Women’s Hospital published in Science Translational Medicine in January 2023, researchers reveal newly discovered potential to exploit cancer cells in the fight against cancer. Using a “dual-action, cancer-killing vaccine” in an advanced mouse model of glioblastoma, they report “promising results”. This means not only tackling established tumours but seemingly inducing long-term immunity by training the immune system to prevent further cancer. As we explored in a previous post on glioblastoma therapy, glioblastoma is a “complex” and aggressive cancer.
A simple idea
Dr Khalid Shah, director of the Centre for Stem Cell and Translational Immunotherapy (CSTI) and vice chair of research at the Department of Neurosurgery at the Brigham, suggests that the team has “pursued a simple idea”. The intention was to “take cancer cells and transform them into cancer killers and vaccines”.
“Using gene engineering, we are repurposing cancer cells to develop a therapeutic that kills tumour cells and stimulates the immune system to both destroy primary tumours and prevent cancer.”
Although the study focuses on glioblastoma, the overall strategy is believed to be applicable to a wider range of tumours. Dr Shah emphasised that despite the “highly technical” nature of the team’s work, “we never lose sight of the patient”.
“Our goal is to take in innovative but translatable approach so that we can develop a therapeutic, cancer-killing vaccine that ultimately will have a lasting impact in medicine.”
A novel approach
Although many labs are pursuing cancer vaccines, the Brigham suggests that Shah and his colleagues have taken a “distinct” approach. Rather than using inactivated tumour cells, they repurposed living tumour cells.
“Like homing pigeons returning to roost, living tumour cells will travel long distances across the brain to return to the site of their fellow tumour cells.”
Thus, when transformed into “cell killing” agents, they will actively return to the tumour site to wreak havoc. The study describes how the researchers “repurposed the tumour cells from interferon-β (IFN-β) sensitive to resistant using CRIPR-Cas9″. This is a unique gene editing tool that allowed the team to engineer the cells to “release immunomodulatory agents IFN-β and granulocyte-macrophage colony-stimulating factor”.
When tested in mice these therapeutic tumour cells (ThTCs) “eliminated established glioblastoma tumours” by “inducing capase-mediated cancer cell apoptosis, down-regulating cancer-associated fibroblast-expressed platelet-derived growth factor receptor β, and activating antitumour immune cell trafficking and antigen-specific T cell activation signalling”.
Putting the cells to the test
These ThTCs were tested in different mice strains. The team also built a safety switch into the cells, which, when activated, could eradicate them if needed. Brigham describes the therapy as “safe, applicable, and efficacious” in the models.
“While further testing and development is needed, Shah’s team specifically chose this model and used human cells to smooth the path of translating their findings for patient settings.”
This step in the development of a potential therapy is exciting; Brigham calls for further investigations and we look forward to learning more about the possibilities they will hold.
At the World Vaccine Congress in Washington in April we have specific tracks dedicated to the discussion of cancer vaccines, and we anticipate great interest in these debates. To join us, get your tickets today.
