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William J. Gradishar, MD, FACP, FASCO


SITC 2022: Neoantigen-Specific Antibody Responses in Metastatic Triple-Negative Breast Cancer

By: Emily Rhode
Posted: Monday, November 21, 2022

A study presented at the 2022 Society for Immunotherapy of Cancer (SITC) Annual Meeting (Abstract 53) and published in the Journal for ImmunoTherapy of Cancer demonstrated the potential benefits of using custom peptide arrays to map neoantigen-specific antibody responses in patients with metastatic triple-negative breast cancer who have been treated with low-dose cyclophosphamide followed by pembrolizumab. The findings indicate a need to better understand the role of tumor antigen-specific antibodies in tumor growth restriction and immunotherapy response, concluded Eric Routh, PhD, of the University of North Carolina Lineberger Comprehensive Cancer Center, Chapel Hill, and colleagues.

“Measures of cumulative antibody signal intensity relative to immunotherapy treatment showed that the one complete responder in the trial had the greatest increase in total antibody signal, which supports a putative association between immune checkpoint blockade–dependent antibody boosting and clinical response,” the study authors noted.

In this study, 40 patients with metastatic triple-negative breast cancer underwent treatment to examine the efficacy of regulatory T-cell depletion with cyclophosphamide plus PD-1 inhibition with pembrolizumab. Based on their clinical responses to this trial, 11 patients were chosen for multiplex enzyme-linked immunosorbent assay (ELISA) peptide array analysis of tumor antigen-specific antibody responses. Further analysis focused on protein subcellular localization, RNA expression, and boostable antibody response to immunotherapy.

The investigators reported that a minority of predicted linear epitopes were associated with antibody signal. Both mutated and self-epitopes were found to be associated with antibody signal. However, the study showed no association between antibody signal and RNA expression of parent proteins or subcellular localization. The team also observed patient-specific patterns of antibody signal boostability that were independent of clinical response.

One complete responder showed an antibody boost that the investigators attributed to increased levels of immunoglobulin G unique to N-terminal residues of native EGFR pathway substrate 8. This finding was surprising because structural protein prediction analysis showed that the region of EGFR pathway substrate 8 targeted by the antibody was not predicted to bind to anything.

Disclosure: For study funding information, visit

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