Clinical trials evaluate T-cell transfer therapy for cancers with a mutated KRAS gene


KRAS protein structure
Photo courtesy of NCI Visuals Online

Patients with KRAS mutations and a specific tissue type may be eligible to participate in new clinical trials at the NIH Clinical Center.

James Yang, M.D., Senior Investigator in the Surgery Branch, has developed an experimental therapy targeting certain cancers that have one of the two most common mutations in a protein called KRAS. KRAS is a gene that sends on/off growth signals to cells. When the KRAS gene changes, or mutates, the “off” signal is disrupted, allowing cell growth to be continuously “on,” which can lead to cancer. KRAS mutations are present in up to a quarter of all human cancers.

Patients in this study will undergo gene transfer therapy that uses their own blood cells. A certain type of white blood cell will be extracted from a patient and multiplied, then a gene will be inserted for one of two receptors, anti-KRAS G12D or anti-KRAS G12V, that can recognize and target these KRAS mutations in cancer cells. These modified white blood cells will then be infused back into the patient. 

The first phase of these studies will determine the highest dose of anti-KRAS T cells that is safe. In the second phase, patients will be treated with the safe dose. Investigators want to see if anti-KRAS T cells can make tumors shrink and whether this therapy has tolerable side effects. Before enrolling, patients will be tested for their HLA type. Only patients with the HLA-A11 molecule are eligible to participate in these studies. identifier: NCT03745326
NCI Protocol ID: NCI-19-C-0017
Official Title: Phase I/II Study Administering Peripheral Blood Lymphocytes Transduced With a Murine T-Cell Receptor Recognizing the G12D Variant of Mutated RAS in HLA-A*11:01 Patients identifier: NCT03190941
NCI Protocol ID: NCI-17-C-0113
Official Title: Administering Peripheral Blood Lymphocytes Transduced With a Murine T-Cell Receptor Recognizing the G12V Variant of Mutated RAS in HLA-A*11:01 Patients

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Summary Posted: Sat, 12/01/2018