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Testing Targeted Therapies in Cancer using Structural DNA Alteration Analysis and Patient-Derived Xenografts

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Published on: July 25, 2020

Engineering Cancer/Testis Antigens With Reversible S-Cationization to Evaluate Antigen Spreading.

Ai Miyamoto¹, Tomoko Honjo¹, Mirei Masui¹

¹Department of Interdisciplinary Science and Engineering in Health Systems, Okayama University, Okayama, Japan.

Frontiers in Oncology

|May 23, 2022

Summary

Quantitative detection of serum autoantibodies to cancer/testis antigens (CTAs) using the MUSCAT assay system can monitor antitumor immune responses. This system aids in evaluating cancer immunotherapy efficacy and clinical outcomes, particularly in gene therapy trials.

Keywords:

autoantibody biomarker cancer-immunity cycle cancer/testis antigens immune monitoring protein engineering

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Area of Science:

Immunology
Oncology
Biotechnology

Background:

Serum autoantibodies to cancer/testis antigens (CTAs) are key biomarkers of antitumor immunity.
Current detection methods face challenges with recombinant CTA protein aggregation.
Multiplexed detection is crucial for assessing immune status and monitoring therapy responses.

Purpose of the Study:

To develop a quantitative, multiplexed assay system for detecting serum autoantibodies to CTAs.
To validate the assay's performance using positive controls and clinical samples.
To evaluate the utility of anti-CTA autoantibody monitoring in cancer immunotherapy.

Main Methods:

Utilized cysteine residue-specific S-cationization to prepare water-soluble, full-length CTAs.
Developed a multiple S-cationized antigen-immobilized bead array (MUSCAT) system with Luminex technology.
Employed rabbit polyclonal antibodies as positive controls for assay validation.

Main Results:

The MUSCAT assay successfully detected immobilized and endogenous CTAs.
Assay results were confirmed by rabbit polyclonal antibodies, showing dynamic ranges.
Autoantibody responses in a gene therapy trial correlated with clinical outcomes, with upregulation preceding tumor regression.

Conclusions:

The MUSCAT assay provides a quantitative method for monitoring anti-CTA autoantibody biomarkers.
This system is valuable for evaluating the cancer-immunity cycle and cancer immunotherapy.
A quality-certified monitoring system can significantly aid in developing and assessing novel cancer therapies.