Adding to their already thick armor, cancer cells are capable of ‘self-homing’ behavior where cells released into the circulation can return to the main tumor site. Therefore, much research has been done to harness this behavior to use the ‘homing’ cancer cells to deliver therapies to indigenous tumors. Now, a study led by researchers at the Brigham and Women’s Hospital leverages the power of gene editing to engineer self-targeting tumor cells designed to kill the main tumor and not destroy themselves. The team states conversely, the engineered cells can be eliminated on demand using a drug to prevent them from rejoining the tumor site. The study is published in the journal Science Translational Medicine.
Previous studies have shown cell-based therapies hold tremendous promise for delivering therapeutic agents to tumors and may provide treatment options where standard therapy has failed. In particular, tumor cells engineered to express therapeutic agents have shown promise to treat cancer, however, their potential to target cell surface receptors specific to the tumor site and their post-treatment fate have not been explored. The current study engineers therapeutic tumor cells expressing ligands specific to primary and recurrent tumor sites, able to induce main tumor-site death without damaging themselves.
The current study utilizes pre-engineered tumor 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 engineered cells were then transferred back into mouse models of brain cancer and breast cancer.
Results demonstrate direct migration of engineered cells to the sites of tumors, and evidence the engineered cells specifically targeted and killed recurrent and metastatic cancer in the mice. Data findings show the treatment increased the survival of the mice, with the engineered cells equipped with a kill switch activated after treatment. PET imaging verified this kill switch successfully eliminated the engineered cancer cells.
The team surmises their study illustrates the therapeutic potential of using engineered tumor cells and their self-homing properties for developing receptor-targeted therapeutics for various cancers. For the future, the researchers state harnessing this power could overcome drug delivery challenges, helping get therapeutics to tumor sites that may otherwise be difficult to reach.
Source: Brigham and Women’s Hospital
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