Researchers from the University of California, San Francisco (UCSF), and Northwestern Medicine may have found a way to circumvent the limitations of modified T lymphocytes by borrowing a few tricks from cancer itself. The new technique used has made human T lymphocytes 100 times more efficient at killing cancer cells.
By studying mutations in malignant T lymphocytes causing lymphoma, they identified a mutation that conferred exceptional efficiency to the modified T lymphocytes. Inserting a gene coding for this unique mutation into normal human T lymphocytes made them over 100 times more efficient at killing cancer cells without any signs of toxicity.
While current immunotherapies only work against blood and bone marrow cancers, the T lymphocytes modified by Northwestern and UCSF were capable of killing tumors derived from the skin, lungs, and stomach in mice. The team has already started working on testing this new approach in humans.
"We used nature's roadmap to improve T lymphocyte therapies," said Dr. Jaehyuk Choi, an associate professor of dermatology and of biochemistry and molecular genetics at the Northwestern University Feinberg School of Medicine. "The superpower that makes cancer cells so strong can be transferred into T lymphocyte therapies to make them powerful enough to eliminate what were once incurable cancers."
"The mutations underlying the resilience and adaptability of cancer cells can empower T lymphocytes to survive and thrive in the harsh conditions created by tumors," said Kole Roybal, an associate professor of microbiology and immunology at UCSF, director of the Parker Institute for Cancer Immunotherapy at UCSF.
Creating effective immunotherapies has, until now, proven difficult against most cancers because the tumor creates an environment focused on its maintenance, diverting resources such as oxygen and nutrients to its advantage. Often, tumors divert the body's immune system, pushing it to defend the cancer instead of attacking it. This not only harms the ability of ordinary T lymphocytes to target cancer cells but also compromises the efficacy of modified T lymphocytes used in immunotherapies, which quickly deplete against the defenses of the tumor.
"For cell-based treatments to work under these conditions," said Roybal, "we must endow healthy T lymphocytes with capabilities beyond what they can naturally achieve." The Northwestern and UCSF teams then examined 71 mutations found in patients with T-cell lymphoma and identified those that could enhance the therapies of modified T lymphocytes in mouse tumor models. Eventually, they isolated one that proved both powerful and non-toxic, submitting it to a rigorous series of safety tests.
"Our findings enable T lymphocytes to kill multiple types of cancer," said Choi, a member of the Robert H. Lurie Comprehensive Cancer Center at Northwestern University. This approach seems to work better than anything discovered to date.
Article Author: Cédric DEPOND