Identification of Tumor Antigens in Ovarian Cancers Using Local and Circulating Tumor-Specific Antibodies

Abstract

Ovarian cancers include several disease subtypes and patients often present with advanced metastatic disease and a poor prognosis. New biomarkers for early diagnosis and targeted therapy are, therefore, urgently required. This study uses antibodies produced locally in tumor-draining lymph nodes (ASC probes) of individual ovarian cancer patients to screen two separate protein microarray platforms and identify cognate tumor antigens. The resulting antigen profiles were unique for each individual cancer patient and were used to generate a 50-antigen custom microarray. Serum from a separate cohort of ovarian cancer patients encompassing four disease subtypes was screened on the custom array and we identified 28.8% of all ovarian cancers, with a higher sensitivity for mucinous (50.0%) and serous (40.0%) subtypes. Combining local and circulating antibodies with high-density protein microarrays can identify novel, patient-specific tumor-associated antigens that may have diagnostic, prognostic or therapeutic uses in ovarian cancer.

PNMA2 forms non-enveloped virus-like capsids that trigger paraneoplastic neurological syndrome

“…We next determined whether PNMA2's virus-like properties are responsible for eliciting autoantibody production. Since PNMA2 appears to be exclusively expressed in neurons of the CNS (Figure 1b, Supplemental Figure 1), we hypothesize that aberrant expression of PNMA2 in tumor cells (8)(9)(10)(11)(12)37) and release of capsids outside of the CNS may be immunogenic. Virus capsids induce a stronger immune response than soluble proteins due to the capsid's influence on antigen transport, adaptive immune response, and cross-presentation (38)(39)(40)(41).…”

“…Patients with elevated levels of PNMA1 (Ma1) or PNMA2 (Ma2) autoantibodies experience limbic/brainstem encephalitis and cerebellar degeneration (5). These patients often present with solid peripheral tumors (1, 6, 7) that are a potential source of PNMA protein (8)(9)(10)(11) and antibodies to PNMA proteins can be diagnostic of specific cancers (12). Prognosis in this paraneoplastic syndrome is poor (7).…”

Serum autoantibody profiling of oral squamous cell carcinoma patients reveals NUBP2 as a potential diagnostic marker

“…Further, they can serve as prognostic markers, as in the case of early-stage non-small cell lung cancer (NSCLC) (21), or as predictive markers for immunotherapy response, for example, to observe anti-PD1 therapy response in alveolar soft part sarcoma (NASPS), NSCLC and lymphoma (53). Autoantibody profiling is being increasingly used to study TAAb signatures in various cancers, including lung (21), melanoma (54), gastric (55), thyroid (56), and ovarian cancers (57).…”

Recent history of Veterinary Immunology in Australia

“…As well as increasing our understanding of immunity against the major sheep parasites, these studies led to the discovery of a novel technique for identifying stage‐specific antigens using antibodies secreted by in vivo ‐induced antibody‐secreting cells 7 . This “ASC‐probe” technology was used to identify vaccine candidates against bacterial (John Walker) 8 and helminth (Vern Bowles, Hamish McWilliam) 9,10 infections and, more recently, tumor‐associated antigens 11 . Immunological studies of the ovine placenta revealed the dramatic increase of a highly granular γδ T‐cell population at late stages of pregnancy with antimicrobial and cytotoxic properties, indicating their role in the protection of the womb during parturition 12 .…”