Development and Characterization of Mouse Anti-canine PD-L1 Monoclonal Antibodies and Their Expression in Canine Tumors by Immunohistochemistry

Overview

Journal Vet Q

Specialty Veterinary Medicine

Date 2023 Jul 21

PMID 37477617

Authors

Sirintra Sirivisoot

Chatikorn Boonkrai

Tossapon Wongtangprasert

Tanapati Phakham

Phijitra Muanwein

Trairak Pisitkun

Chenphop Sawangmake

Araya Radtanakatikanon

Anudep Rungsipipat

Affiliations

Soon will be listed here.

Abstract

Immune escape is the hallmark of carcinogenesis. This widely known mechanism is the overexpression of immune checkpoint ligands, such as programmed cell death protein 1 and programmed death-ligand 1 (PD-1/PD-L1), leading to T cell anergy. Therefore, cancer immunotherapy with specific binding to these receptors has been developed to treat human cancers. Due to the lack of cross-reactivity of these antibodies in dogs, a specific canine PD-1/PD-L1 antibody is required. The aim of this study is to develop mouse anti-canine PD-L1 (cPD-L1) monoclonal antibodies and characterize their properties. Six mice were immunized with recombinant cPD-L1 with a fusion of human Fc tag. The hybridoma clones that successfully generated anti-cPD-L1 antibodies and had neutralizing activity were selected for monoclonal antibody production. Antibody properties were tested by immunosorbent assay, surface plasmon resonance, and immunohistochemistry. Four hybridomas were effectively bound and blocked to recombinant cPD-L1 and cPD-1-His-protein, respectively. Candidate mouse monoclonal antibodies worked efficiently on formalin-fixed paraffin-embedded tissues of canine cancers, including cutaneous T-cell lymphomas, mammary carcinomas, soft tissue sarcomas, squamous cell carcinomas, and malignant melanomas. However, functional assays of these anti-cPD-L1 antibodies need further investigation to prove their abilities as therapeutic drugs in dogs as well as their applications as prognostic markers.

Citing Articles

A Review on Canine and Human Soft Tissue Sarcomas: New Insights on Prognosis Factors and Treatment Measures.

DellAnno F, Giugliano R, Listorti V, Razzuoli E Vet Sci. 2024; 11(8).

PMID: 39195816 PMC: 11358912. DOI: 10.3390/vetsci11080362.

Single nucleotide polymorphism profiles of canine T-cell and null-cell lymphomas.

Sirivisoot S, Kasantikul T, Techangamsuwan S, Rungsipipat A Front Vet Sci. 2024; 11:1439706.

PMID: 39176397 PMC: 11339873. DOI: 10.3389/fvets.2024.1439706.

Canine Mammary Cancer: State of the Art and Future Perspectives.

Vazquez E, Lipovka Y, Cervantes-Arias A, Garibay-Escobar A, Haby M, Queiroga F Animals (Basel). 2023; 13(19).

PMID: 37835752 PMC: 10571550. DOI: 10.3390/ani13193147.

References

Maekawa N, Konnai S, Okagawa T, Nishimori A, Ikebuchi R, Izumi Y . Immunohistochemical Analysis of PD-L1 Expression in Canine Malignant Cancers and PD-1 Expression on Lymphocytes in Canine Oral Melanoma. PLoS One. 2016; 11(6):e0157176. PMC: 4898770. DOI: 10.1371/journal.pone.0157176. View

Shosu K, Sakurai M, Inoue K, Nakagawa T, Sakai H, Morimoto M . Programmed Cell Death Ligand 1 Expression in Canine Cancer. In Vivo. 2016; 30(3):195-204. View

Jubel J, Barbati Z, Burger C, Wirtz D, Schildberg F . The Role of PD-1 in Acute and Chronic Infection. Front Immunol. 2020; 11:487. PMC: 7105608. DOI: 10.3389/fimmu.2020.00487. View

Ambrosius L, Dhawan D, Ramos-Vara J, Ruple A, Knapp D, Childress M . Quantification and prognostic value of programmed cell death ligand-1 expression in dogs with diffuse large B-cell lymphoma. Am J Vet Res. 2018; 79(6):643-649. DOI: 10.2460/ajvr.79.6.643. View

Pinard C, Hocker S, Poon A, Inkol J, Matsuyama A, Wood R . Evaluation of PD-1 and PD-L1 expression in canine urothelial carcinoma cell lines. Vet Immunol Immunopathol. 2021; 243:110367. DOI: 10.1016/j.vetimm.2021.110367. View

Maekawa N, Konnai S, Takagi S, Kagawa Y, Okagawa T, Nishimori A . A canine chimeric monoclonal antibody targeting PD-L1 and its clinical efficacy in canine oral malignant melanoma or undifferentiated sarcoma. Sci Rep. 2017; 7(1):8951. PMC: 5567082. DOI: 10.1038/s41598-017-09444-2. View

Igase M, Nemoto Y, Itamoto K, Tani K, Nakaichi M, Sakurai M . A pilot clinical study of the therapeutic antibody against canine PD-1 for advanced spontaneous cancers in dogs. Sci Rep. 2020; 10(1):18311. PMC: 7591904. DOI: 10.1038/s41598-020-75533-4. View

Mittendorf E, Philips A, Meric-Bernstam F, Qiao N, Wu Y, Harrington S . PD-L1 expression in triple-negative breast cancer. Cancer Immunol Res. 2014; 2(4):361-70. PMC: 4000553. DOI: 10.1158/2326-6066.CIR-13-0127. View

Vari F, Arpon D, Keane C, Hertzberg M, Talaulikar D, Jain S . Immune evasion via PD-1/PD-L1 on NK cells and monocyte/macrophages is more prominent in Hodgkin lymphoma than DLBCL. Blood. 2018; 131(16):1809-1819. PMC: 5922274. DOI: 10.1182/blood-2017-07-796342. View

10.

Choi J, Withers S, Chang H, Spanier J, De La Trinidad V, Panesar H . Development of canine PD-1/PD-L1 specific monoclonal antibodies and amplification of canine T cell function. PLoS One. 2020; 15(7):e0235518. PMC: 7332054. DOI: 10.1371/journal.pone.0235518. View

11.

Hartley G, Faulhaber E, Caldwell A, Coy J, Kurihara J, Guth A . Immune regulation of canine tumour and macrophage PD-L1 expression. Vet Comp Oncol. 2016; 15(2):534-549. DOI: 10.1111/vco.12197. View

12.

Latchman Y, Wood C, Chernova T, Chaudhary D, Borde M, Chernova I . PD-L2 is a second ligand for PD-1 and inhibits T cell activation. Nat Immunol. 2001; 2(3):261-8. DOI: 10.1038/85330. View

13.

Murciano-Goroff Y, Betof Warner A, Wolchok J . The future of cancer immunotherapy: microenvironment-targeting combinations. Cell Res. 2020; 30(6):507-519. PMC: 7264181. DOI: 10.1038/s41422-020-0337-2. View

14.

Prat A, Navarro A, Pare L, Reguart N, Galvan P, Pascual T . Immune-Related Gene Expression Profiling After PD-1 Blockade in Non-Small Cell Lung Carcinoma, Head and Neck Squamous Cell Carcinoma, and Melanoma. Cancer Res. 2017; 77(13):3540-3550. DOI: 10.1158/0008-5472.CAN-16-3556. View

15.

Vinay D, Ryan E, Pawelec G, Talib W, Stagg J, Elkord E . Immune evasion in cancer: Mechanistic basis and therapeutic strategies. Semin Cancer Biol. 2015; 35 Suppl:S185-S198. DOI: 10.1016/j.semcancer.2015.03.004. View

16.

Maekawa N, Konnai S, Nishimura M, Kagawa Y, Takagi S, Hosoya K . PD-L1 immunohistochemistry for canine cancers and clinical benefit of anti-PD-L1 antibody in dogs with pulmonary metastatic oral malignant melanoma. NPJ Precis Oncol. 2021; 5(1):10. PMC: 7881100. DOI: 10.1038/s41698-021-00147-6. View

17.

Cascio M, Whitley E, Sahay B, Cortes-Hinojosa G, Chang L, Cowart J . Canine osteosarcoma checkpoint expression correlates with metastasis and T-cell infiltrate. Vet Immunol Immunopathol. 2021; 232:110169. DOI: 10.1016/j.vetimm.2020.110169. View

18.

Yamazaki T, Akiba H, Iwai H, Matsuda H, Aoki M, Tanno Y . Expression of programmed death 1 ligands by murine T cells and APC. J Immunol. 2002; 169(10):5538-45. DOI: 10.4049/jimmunol.169.10.5538. View

19.

Nemoto Y, Shosu K, Okuda M, Noguchi S, Mizuno T . Development and characterization of monoclonal antibodies against canine PD-1 and PD-L1. Vet Immunol Immunopathol. 2018; 198:19-25. DOI: 10.1016/j.vetimm.2018.02.007. View

20.

Maekawa N, Konnai S, Ikebuchi R, Okagawa T, Adachi M, Takagi S . Expression of PD-L1 on canine tumor cells and enhancement of IFN-γ production from tumor-infiltrating cells by PD-L1 blockade. PLoS One. 2014; 9(6):e98415. PMC: 4051644. DOI: 10.1371/journal.pone.0098415. View