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Updated: Sep 29, 2025

Analyzing Tumor and Tissue Distribution of Target Antigen Specific Therapeutic Antibody
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Tumor-reactive antibodies evolve from non-binding and autoreactive precursors

Roei D Mazor1, Nachum Nathan2, Amit Gilboa3

  • 1Department of Immunology, Weizmann Institute of Science, Rehovot 7610001, Israel; Department of Biological Regulation, Weizmann Institute of Science, Rehovot 7610001, Israel.

Cell
|March 19, 2022
PubMed

The tumor microenvironment hosts antibody-secreting cells (ASCs) associated with a favorable prognosis in several types of cancer. Patient-derived antibodies have diagnostic and therapeutic potential; yet, it remains unclear how antibodies gain autoreactivity and target tumors. Here, we found that somatic hypermutations (SHMs) promote antibody antitumor reactivity against surface autoantigens in high-grade serous ovarian carcinoma (HGSOC). Patient-derived tumor cells were frequently coated with IgGs. Intratumoral ASCs in HGSOC were both mutated and clonally expanded and produced tumor-reactive antibodies that targeted MMP14, which is abundantly expressed on the tumor cell surface. The reversion of monoclonal antibodies to their germline configuration revealed two types of classes: one dependent on SHMs for tumor binding and a second with germline-encoded autoreactivity. Thus, tumor-reactive autoantibodies are either naturally occurring or evolve through an antigen-driven selection process. These findings highlight the origin and potential applicability of autoantibodies directed at surface antigens for tumor targeting in cancer patients.

Keywords:
B cellsHGSOCMMP14MT1-MMPantibodiesantibody-mediated immune responseautoantibodiescancerovarian cancerplasma cells

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