Fight cancer with ready-made therapeutic T cells that do not cause rejection

Personalized cancer treatment is no longer a future option. In the last few years, researchers have made great strides in “teaching” the body’s immune T cells to recognize and kill specific cancer cells, and human clinical trials have shown that this approach can successfully eliminate tumors. I showed you.

Cancer patients today may be part of the following clinical scenarios: The patient comes to the hospital and doctors and scientists analyze and identify the tumor cancerSpecific markers that are targets for new therapies. Blood is collected from the patient and sent to the Cell and Gene Therapy Center at Baylor College of Medicine. There, immune T cells are transformed into cells with the mission of identifying and killing cells with tumor-specific tags. The final cells are injected into the patient’s body to complete the task.

“Our center will genetically engineer the patient’s T cells with the tools necessary to identify the patient’s tumor-specific markers and eliminate the cancer,” said Pathology and Immunology Associate Professor. Baylor’s Cell and Gene Therapy Center.

Although this treatment can effectively eliminate the tumor, T-cell “training” is complex and expensive. “Sometimes trained T cells aren’t very potent, because patients are given many therapies that weaken the immune cells we work with,” Mamonkin said.

In addition, the process of producing therapeutic T cells is time consuming. “It can take weeks to prepare T cells, which may worsen the patient,” Mamonkin said.

Next steps: Ready-made treatments

“Since we have found many possibilities for this type of cellular immunotherapy, the next step is to streamline it, make it accessible, and make sure that the resulting T cells have the highest potency. “Momkinkin said. Dan L Duncan Member of Comprehensive Cancer Center.

Researchers are developing ready-made, ready-to-use therapeutic T cells. These are genetically engineered T cells produced from normal, healthy donors. The cells have been expanded, well characterized, and shown to be effective in killing cancer cells. Cells are stored frozen until use and frozen in liquid nitrogen. In this scenario, cancer patients come to the hospital to identify tumor markers. Next, with the identification information of the tumor-specific tag in hand, the doctor went to a room filled with a large subzero freezer, where healthy immune T cells genetically engineered to recognize and destroy cells were Look for a freezer that holds a small container containing the patient’s cancer-specific marker. These “off-the-shelf” off-the-shelf cells are thawed, prepared and injected into the patient a few days later.

“This approach overcomes the two limitations of the original approach, which avoids the time-consuming and complex steps of training and expanding patient cells, resulting in higher potency therapeutic T cells,” Mamonkin. He said. “But this novel approach has a new set of limitations.”

Dealing with rejection

One of the limitations of the off-the-shelf approach appears when therapeutic T cells enter the patient’s body. The patient’s own immune system may recognize cells as foreign and reject therapeutic cells, as occurs with organ transplants.

“This is a major issue because rejection not only shortens the duration of T cell activity against the tumor, but also prevents subsequent administration of cells. The immune system rejects subsequent administration of cells in the correct way. ”, Fei Yang Mo, graduate student in Mamonkin’s lab. “To solve this problem, we thought that the best defense was a good attack.” Researchers gave therapeutic T cells a tool that would allow them to repel a patient’s attack. Was Immune cells To them. They engineered therapeutic T cells to express a receptor called the allo-immunoprotective receptor or ADR. ADR recognizes a specific molecule called 4-1BB. It is only expressed on activated T cells in patients and on natural killer (NK) cells that attack them. 4-1BB is not expressed on resting T and NK cells that do not retrograde to therapeutic T cells.

“Both laboratory and animal model studies with hematological cancers or solid tumors have shown that ADR prevents rejection of ready-made therapeutic T cells,” Mo said. “They not only resisted rejection, but expanded and lasted longer than therapeutic T cells without ADR. They plan to conduct a clinical trial in 2021.

Beyond cancer applications

“If successful, this approach will cause T-cellIt’s like rejecting transplanted organs, mediating graft-versus-host disease, or perpetuating autoimmunity,” Mamonkin said. “We are very pleased to be able to develop this concept for several applications other than cancer treatment.” This technology is licensed for fate treatment. A clinical stage biopharmaceutical company planning to integrate ADR into clinical products.

“The BCM Ventures team is excited to partner with Fate Therapeutics in the lighting community to support the implementation of ADR technology developed at BCM’s Mamonkin Labs. , And now it will be more widely used in clinical settings to benefit patients,” said Michael Dilling, director of the Baylor Licensing Group. “BCM is an innovator in the development of cell therapy and the commercial sector is increasingly focusing on BCM as a source of new innovation.”