Application in immuno oncology
Context and Problem:
Monoclonal antibody–based treatments have revolutionized the treatment of a large number of cancers. For example, through the use of monoclonal therapeutics, the 5-year survival rate for patients with metastatic melanoma has increased significantly, from less than 5% with chemotherapy alone to 20% with ipilimumab (Yervoy) monotherapy to 52% for patients receiving the combination of nivolumab (Opdivo) and ipilimumab. While these dramatic results have provided hope to millions, these treatments are not universally effective. Some patients fail to respond, and there is currently no method to determine who would respond to a given treatment regimen. As being able to determine whether a given treatment regimen will be successful for patient before the treatment is given is critical, Systems Serology was used to determine if there were antibody features that could predict successful treatment with ipilimumab.
Systems Serology Application:
Pre-treatment features of tumor-specific antibodies can separate responders from non-responders
In a pilot proof-of-concept study, a small cohort of ipilimumab-treated melanoma patients, half of whom responded to ipilimumab, were retrospectively profiled using Systems Serology. To identify potential antibody features that could predict treatment success, serum samples collected prior to starting ipilimumab treatment were profiled against a panel of known melanoma tumor antigens or melanoma cell line isolates. Interestingly, prior to beginning ipilimumab treatment, the patients who responded to ipilimumab had a distinct antibody profile compared to the patients where ipilimumab failed to control tumor progression. While preliminary, these results suggest that it may be possible to predict if a treatment will be successful based on antibody profiles. Ongoing studies aim to validate this signature and determine if similar signatures exist across other tumor types and treatments.
Conclusions and future directions:
Long thought to be limited to the control of infections, the role of antibodies in the diagnosis, treatment, and control of cancer is increasingly being recognized. Tumor-infiltrating B cells have been shown to produce tumor-reactive antibodies, which are detectable in the blood of cancer patients. Importantly, these tumor-infiltrating B cells have been linked to favorable prognoses across a number of tumors, and antibodies from these cells can drive tumor regression. Likely critical to the activity of these naturally occurring or vaccine-induced antibodies are the myriad of Fc-mediated functions that antibodies can induce.
The Systems Serology suite of assays offered by SeromYx has broad potential applications in this space, from aiding in the development of novel cancer vaccines and therapeutics as well as guiding personalizing patient care with existing therapeutics. Systems Serology can also be used to identify the antibody features and functions that are associated with the clearance of virus-induced tumors, such as human papillomavirus–associated cervical carcinoma or Epstein-Barr virus–associated lymphoma, as well as evaluating the antibody response to neoantigen-based vaccines to identify antibody functions that may be associated with tumor remission. This information can then be used to guide the design of more effective vaccines and monoclonal therapeutics. Similarly, Systems Serology can be used to identify antibody features that can predict successful treatment or identify features linked to ongoing successful treatment. These antibody biomarkers could then be used to identify patients who would best respond to particular therapies or be used to easily monitor treatment progression. SeromYx is actively seeking collaborators to work with on pilot studies: please contact the CEO to discuss.