[ad_1]
A new imaging test looks promising for identifying patients with kidney cancer likely to benefit from immunotherapy.
In a study published today in the Journal of Cancer Immunotherapy, researchers at the Kidney Cancer Program at the South West Medical Center of UT have come up with a new test to shed light on kidney cancers that may respond to checkpoint inhibitors.
The strategy was to transform an immunotherapy drug, atezolizumab (Tecentriq, Genentech Group / Roche), into a diagnostic tracer. Atezolizumab, which is used to treat lung, bad and bladder cancer, binds to PD-L1, which it disables, a protein that cancer cells present on the surface to block killer immune cells. By labeling atezolizumab with zirconium 89 (Zr89), a radioactive metal generated with the aid of a cyclotron, researchers were able to visualize atezolizumab using PET (emission tomography). of positrons). As such, a very small dose of Zr89-atezolizumab can be used to badess whether tumors deploy PD-L1 to suppress immune cells and whether drugs that deactivate this pathway can be effective.
Currently, immunotherapy drugs benefit less than 50% of patients with kidney cancer. With immuno-PET, or iPET, as a screening tool, the investigators hope to identify the patients who will benefit. Marking the first time that this type of theranostic (drug converted into diagnostic test) is used for kidney cancer, the approach opens a molecular window on what happens in a patient with cancer.
In proof-of-principle experiments, a team led by Dr. James Brugarolas, one of the corresponding authors of the study and director of the UT Southwestern Kidney Cancer Program, has shown that the Zr89 -azolizumab was able to illuminate high-grade kidney tumors. PD-L1. In the study, the researchers selected tumors from two patients, one with a high PD-L1 level and the other with a low PD-L1 level, and transplanted into mice. . The mice then received intravenous Zr89-atezolizumab and were evaluated by PET. As predicted by mouse studies, the patient with a high PD-L1 tumor experienced a significant regression of his metastases when he was treated with nivolumab (Opdivo, Bristol-Myers Squibb), which targets the PD-L1 pathway.
The development of tests to predict which patients will respond to immunotherapy is essential. "
Dr. Hans Hammers, Immunotherapy Expert of the Kidney Cancer Program
Zr89-Atezolizumab has been filed with the US Food and Drug Administration by the Cyclotron and Radiochemistry Program led by Dr. Xiankai Sun of UT Southwestern, also corresponding author of the study, and is currently undergoing a review. evaluation in patients participating in a clinical trial at UT. Harold C. Simmons Comprehensive Cancer Center Southwestern.
The clinical trial is made possible thanks to a $ 600,000 translation prize awarded to Dr. Brugarolas' team by the V Foundation for Cancer Research. The preclinical studies were funded by a grant from the SPORE (Specialized Research Program) of the National Cancer Institute.
We hope that the IPET will identify patients with kidney cancer likely to benefit from checkpoint inhibitors. "
Alex Bowman, principal investigator of the clinical trial, with Drs Brugarolas and Orhan Öz.
A second trial is also planned at the Simmons Cancer Center, using Zr89-atezolizumab, to evaluate the impact of stereotaxic body radiation on the expression of PD-L1 in patients with kidney cancer.
"The SBRT has the potential to induce inflammation and activate an immune response, and we are excited to further evaluate this treatment in patients using iPET," said the Dr. Raquibul Hannan, a leader in radiation therapy for kidney cancer and the principal investigator of the study. The SBRT trial will be funded by the Congress-led Kidney Cancer Research Program.
Source:
UT Southwestern Medical Center
Journal reference:
Brugarolas, J. et al. (2019) Detection of PD-L1 using immuno-PET immuno-PET 89Zr-atezolizumab in renal cell carcinoma tumors of a patient with a favorable response to nivolumab. Journal of Cancer Immunotherapy. doi.org/10.1186/s40425-019-0607-z.
[ad_2]
Source link
