October 11, 2021 | News & Notices
Mass spectrometry technology contributed to a biomarker discovery for antibody therapeutics in cancer immunotherapy
Discovering a Biomarker for the Clinical Outcome of Cancer Patients treated with ipilimumab by Providence Cancer Institute, USA and Shimadzu Corporation
Shimadzu Corporation (Shimadzu) collaborated with Drs. William Redmond and Yoshinobu Koguchi of the Providence Cancer Institute (Portland, Oregon, USA) to find a biomarker for the clinical outcome of cancer patients treated with anti-CTLA-4 antibody ipilimumab (YERVOY®)*1.
Shimadzu analyzed the blood concentration of the immune checkpoint inhibitor ipilimumab using mass spectrometry and nSMOL Antibody BA Kit. Ipilimumab is a therapeutic antibody that blocks an inhibitory immune checkpoint molecule called CTLA-4. While it has shown high therapeutic efficacy, CTLA-4 blockade often causes severe immune-related adverse events (irAEs). Therefore, stratifying patients based on information regarding who will likely respond to ipilimumab has been a major clinical challenge.
In this study, we found that the serum trough levels of ipilimumab were significantly associated with clinical responses for the treatment of advanced melanoma with ipilimumab. In combination with other inflammatory cytokines*2, serum levels of ipilimumab may serve as a biomarker associated with the clinical outcome of patients with advanced melanoma treated with ipilimumab.
“We are excited about this novel approach that may help inform which patients will benefit from ipilimumab immunotherapy” said Dr. Redmond, Member and Director, Immune Monitoring Laboratory, at the Earle A. Chiles Research Institute, a division of Providence.
Since 2018, Providence and Shimadzu have been working together to develop technologies to identify mutation-derived unique tumor antigens for personalized immunotherapy (neoantigens) and to determine the pharmacokinetics of therapeutic antibodies in cancer immunotherapy. This study highlights the potential utility of mass spectrometry technologies to explore biomarkers of response following immunotherapy for cancer patients.
*1 A therapeutic antibody that induces anticancer effects by inhibiting the antigen (cytotoxic T-lymphocyte-associated protein 4, CTLA-4) recognized by cytotoxic T-lymphocytes, thereby re-invigorating the function of T cells.
*2 chemokine CXCL11 (CXCL11, a molecule that causes migration of activated T cells) and interleukin 6 (IL-6, an indicator of immune inflammation).
For more information, please refer to the following original paper published in Journal for Immunotherapy of Cancer.
Trough levels of ipilimumab in serum as a potential biomarker of clinical outcomes for patients with advanced melanoma after treatment with ipilimumab
Koguchi Y, Iwamoto N, Shimada T, Chang SC, Cha J, Curti BD, Urba WJ, Piening BD, and Redmond WL
Journal for Immunotherapy of Cancer.
https://jitc.bmj.com/content/9/10/e002663
About Providence Cancer Institute
Providence Cancer Institute, a part of Providence St. Joseph Health, offers the latest in cancer services, including diagnostic, treatment, prevention, education, support and internationally renowned research. Providence Cancer Institute is home to the Earle A. Chiles Research Institute, a world-class research facility located within the Robert W. Franz Cancer Center in Portland, Oregon, and is a recognized leader in the field of cancer immunotherapy since 1993. Investigators lead more than 400 active clinical trials in key areas such as cancers of the: breast, colon/rectum, prostate, lung, esophagus, liver and pancreas, head and neck, ovary, skin and blood. Other studies are investigating treatments for COVID-19. Learn more at providenceoregon.org/cancer.