Engineered cancer cells can track and destroy tumours.


It is known that cancer cells exhibit a ‘self-homing’ behaviour whereby cells released into the circulation can return to the main tumour site. Therefore, much research has been done to harness this behaviour and use the cells to deliver therapies to the indigenous tumours.  Now, a study led by researchers at Brigham and Women’s Hospital leverages the power of gene editing to engineer self-targeting tumour cells designed to kill the main tumour and not destroy themselves. The team state that conversely, the engineered cells could be eliminated on demand using a drug to prevent them from rejoining the tumour site.  The study is published in the journal Science Translational Medicine.

Previous studies show that cell-based therapies hold tremendous promise for delivering therapeutic agents to tumours and may provide treatment options where standard therapy has failed.   In particular, tumour cells engineered to express therapeutic agents have shown promise to treat cancer, however, their potential to target cell surface receptors specific to the tumour site and their post treatment fate have not been explored.  The current study engineers therapeutic tumour cells expressing ligands specific to primary and recurrent tumour sites, which induce main tumour-site death without damaging themselves.

The current study utilises pre-engineered tumour cells to match the patient’s HLA phenotype, and uses CRISPR to edit the genome of a patient’s cancer cells and insert therapeutic molecules; these cells were then transferred back into mouse models of brain cancer and breast cancer which has spread to the brain.

Results show direct migration of engineered cells to the sites of tumours, and evidence that the engineered cells specifically targeted and killed recurrent and metastatic cancer in the mice. Data findings show that the treatment increased the survival of the mice, with the engineered cells equipped with a kill switch which could be activated after treatment; PET imaging showed that this kill switch worked to eliminate the engineered cancer cells.

The team surmise their study demonstrates the therapeutic potential of using engineered tumour cells and their self-homing properties for developing receptor-targeted therapeutics for various cancers.  For the future, the researchers state that harnessing this power could overcome drug delivery challenges, helping get therapeutics to tumour sites that may otherwise be difficult to reach.

Source: Brigham and Women’s Hospital

 

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