Antitumor effect of plant-produced anti-CTLA-4 monoclonal antibody in a murine model of colon cancer
Monoclonal antibody
anti-CTLA-4 antibody
Cytotoxic T cell
Immunology
Cancer immunotherapy
Plant Science
Chimeric Antigen Receptor T Cell Therapy
Cancer research
Biochemistry
Cancer Immunotherapy
SB1-1110
In vitro
Biochemistry, Genetics and Molecular Biology
Health Sciences
In vivo
Nicotiana benthamiana
cytotoxic T lymphocyte-associated protein 4
Biology
Antibody
Immunology and Microbiology
cancer immunotherapy
FOS: Clinical medicine
Production of Recombinant Pharmaceuticals in Plants
Plant culture
Life Sciences
T cell
Ipilimumab
3. Good health
Ex vivo
Immunotoxin Therapy for Cancer Treatment
Immune system
Oncology
Antigen
Medicine
CTLA-4
2C8
Immunotherapy
Immune checkpoint
Biotechnology
DOI:
10.3389/fpls.2023.1149455
Publication Date:
2023-08-30T07:09:42Z
AUTHORS (9)
ABSTRACT
Cytotoxic T lymphocyte-associated protein 4 (CTLA-4) is an immune checkpoint regulator exclusively expressed on T cells that obstructs the cell’s effector functions. Ipilimumab (Yervoy®), a CTLA-4 blocking antibody, emerged as a notable breakthrough in modern cancer treatment, showing upfront clinical benefits in multiple carcinomas. However, the exhilarating cost of checkpoint blockade therapy is discouraging and even utmost prominent in developing countries. Thereby, affordability of cancer care has become a point of emphasis in drug development pipelines. Plant expression system blossomed as a cutting-edge platform for rapid, facile to scale-up, and economical production of recombinant therapeutics. Here, we describe the production of an anti-CTLA-4 2C8 antibody in Nicotiana benthamiana. ELISA and bio-layer interferometry were used to analyze antigen binding and binding kinetics. Anticancer responses in vivo were evaluated using knocked-in mice implanted with syngeneic colon tumor. At 4 days post-infiltration, the antibody was transiently expressed in plants with yields of up to 39.65 ± 8.42 μg/g fresh weight. Plant-produced 2C8 binds to both human and murine CTLA-4, and the plant-produced IgG1 also binds to human FcγRIIIa (V158). In addition, the plant-produced 2C8 monoclonal antibody is as effective as Yervoy® in inhibiting tumor growth in vivo. In conclusion, our study underlines the applicability of plant platform to produce functional therapeutic antibodies with promising potential in cancer immunotherapy.
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