Tumor cells are genetically modified to become dual anti-cancer agents. This is an intriguing method that has been successfully tested on mice at Harvard University (USA). Penetrating into their original tumor, these cells, which have become toxic to their former relatives, act both as a cure and as a vaccine against brain cancer.
Fighting cancer with cancer, fire with fire
Cancer cells have a very special ability. “They can travel long distances in the brain to find their own kind,” says researcher Khalid Shah, leader of the new work, published in the journal Science Translational Medicine.
So this is the good old Trojan horse method that researchers have applied to glioblastoma, the most common brain cancer. “Most patients with aggressive brain cancer do not live past 15 to 18 months,” says Khalid Shah. Before that, researchers tried to treat lung cancer, colorectal cancer, or even melanoma with modified cancer cells, but only dead cells, for safety reasons. But the efficiency is very poor. This time the used cancer cells stay alive and are sent back armed against their side in their tumors. “In these aggressive forms of cancer, most cells find a way to hide from treatment or from our immune system. Our idea is to fight cancer with cancer. Fire with fire,” Khalid Shah clarifies.
Kill cancer cells and prevent them from returning
The cells, called ThTCs, are modified with the CRISPR-Cas9 “genetic scissors” to give them the ability to produce large amounts of two small immune system proteins, interferon-beta (or beta-interferon) and colony-stimulating factor, granulocytes and macrophages, which are two types of immune cells (GM-CSF). Interferon has two main effects. On the one hand, it kills tumor cells, and on the other hand, it activates and attracts immune cells on the spot. As for GM-CSF, it stimulates the proliferation and action of dendritic cells, a type of immune cell necessary to activate the acquired immune system, that is, one that protects against threat for a long time. or an infection. Roughly speaking, because in fact their effects potentiate each other, IFN beta treats cancer, and GM-GSF prevents its recurrence, “preparing the immune system for long-term antitumor responses,” the authors explain in the publication.
The trick was to add a few other essential modifications to the selected tumor cells to make them good double agents. First, they themselves must be made insensitive to beta-interferons, otherwise they will commit suicide, wanting to kill their fellows. Then you need a system to kill them once their role is done. To do this, the researchers add a “double safety switch” to ThTC in the form of sensitivity to two molecules that they cannot accidentally encounter.
The tumors of most of the treated mice were eradicated.
The brain tumors in the mice studied are human tumors, which researchers start with surgical removal, as doctors do in real life with 85% of patients with glioblastoma. A procedure that saves time but, unfortunately, does not prevent cancer cells that have lethally escaped from recreating the tumor. “The idea is to encapsulate our modified cells in order to deliver them to the cavity left after the surgical resection,” explains Khalid Shah. The drug is then injected into the site of the tumor and the survival rate of the mice to cancer recurrence is measured.
One week after ThTC treatment, residual tumor cells in the cavity completely disappeared in 10 out of 12 mice! On the other hand, tumors reappeared in the control groups and the animals had to be euthanized 10 days after other treatments. “Our method works very well even against metastases,” that is, when cancer cells separate from their place of origin and spread to other parts of the body, adds Khalid Shah.
Towards a Cancer Vaccine for Severe Cases
Although this method is effective and attractive, it is costly and time consuming since each ThTC treatment must be generated from the tumor of the patient to be treated. Therefore, it would be “difficult to use the ThTC strategy for the primary treatment of glioblastomas,” comment the investigators, who would rather expect use when the disease is “recurrent or metastatic.” “Our goal is to take an innovative yet versatile approach to be able to develop a therapeutic cancer vaccine that has potential beyond glioblastoma and can treat many other types of cancer,” concludes Khalid Shah.