Antibody landscape of C57BL/6 mice cured of B78 melanoma via a combined radiation and immunocytokine immunotherapy regimen

被引:1
|
作者
Hoefges, Anna [1 ]
McIlwain, Sean J. [2 ]
Erbe, Amy K. [1 ]
Mathers, Nicholas [1 ]
Xu, Angie [1 ]
Melby, Drew [1 ]
Tetreault, Kaitlin [2 ]
Le, Trang [2 ]
Kim, Kyungmann [2 ]
Pinapati, Richard S. [3 ]
Garcia, Bradley H. [3 ]
Patel, Jigar [3 ]
Heck, Mackenzie [1 ]
Feils, Arika S. [1 ]
Tsarovsky, Noah [1 ]
Hank, Jacquelyn Ann [1 ]
Morris, Zachary Scott [1 ]
Ong, Irene M. [2 ,4 ]
Sondel, Paul Mark [1 ,5 ]
机构
[1] Univ Wisconsin, Dept Human Oncol, Madison, WI 53706 USA
[2] Univ Wisconsin, Dept Biostat & Med Informat, Madison, WI USA
[3] Nimble Therapeut Inc, Madison, WI USA
[4] Univ Wisconsin, Dept Obstet & Gynecol, Madison, WI USA
[5] Univ Wisconsin, Dept Pediat, Madison, WI 53706 USA
来源
FRONTIERS IN IMMUNOLOGY | 2023年 / 14卷
基金
美国国家卫生研究院;
关键词
high-density peptide array; melanoma; in situ vaccine; radio-immunotherapy; antibody; cancer; proteome; GD2; GANGLIOSIDE; ANTI-GD2; ANTIBODY; CELLS; EPITOPES; IDENTIFICATION;
D O I
10.3389/fimmu.2023.1221155
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Sera of immune mice that were previously cured of their melanoma through a combined radiation and immunocytokine immunotherapy regimen consisting of 12 Gy of external beam radiation and the intratumoral administration of an immunocytokine (anti-GD2 mAb coupled to IL-2) with long-term immunological memory showed strong antibody-binding against melanoma tumor cell lines via flow cytometric analysis. Using a high-density whole-proteome peptide array (of 6.090.593 unique peptides), we assessed potential protein-targets for antibodies found in immune sera. Sera from 6 of these cured mice were analyzed with this high-density, whole-proteome peptide array to determine specific antibody-binding sites and their linear peptide sequence. We identified thousands of peptides that were targeted by these 6 mice and exhibited strong antibody binding only by immune (after successful cure and rechallenge), not naive (before tumor implantation) sera and developed a robust method to detect these differentially targeted peptides. Confirmatory studies were done to validate these results using 2 separate systems, a peptide ELISA and a smaller scale peptide array utilizing a slightly different technology. To the best of our knowledge, this is the first study of the full set of germline encoded linear peptide-based proteome epitopes that are recognized by immune sera from mice cured of cancer via radio-immunotherapy. We furthermore found that although the generation of B-cell repertoire in immune development is vastly variable, and numerous epitopes are identified uniquely by immune serum from each of these 6 immune mice evaluated, there are still several epitopes and proteins that are commonly recognized by at least half of the mice studied. This suggests that every mouse has a unique set of antibodies produced in response to the curative therapy, creating an individual "fingerprint." Additionally, certain epitopes and proteins stand out as more immunogenic, as they are recognized by multiple mice in the immune group.
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页数:20
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