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Updated: May 24, 2026
A Real-time Potency Assay for Chimeric Antigen Receptor T Cells Targeting Solid and Hematological Cancer Cells
Published on: November 12, 2019
Engineering the first chimeric antibody in targeting intracellular PRL-3 oncoprotein for cancer therapy in mice
Ke Guo1, Jing Ping Tang, Li Jie
1Institute of Molecular and Cell Biology, A*STAR, 61 Biopolis Drive, Proteos, Singapore 138648, Republic of Singapore.
Abstract:
Antibodies are considered as 'magic bullets' because of their high specificity. It is believed that antibodies are too large to routinely enter the cytosol, thus antibody therapeutic approach has been limited to extracellular or secreted proteins expressed by cancer cells. However, many oncogenic proteins are localized within the cell. To explore the possibility of antibody therapies against intracellular targets, we generated a chimeric antibody targeting the intracellular PRL-3 oncoprotein to assess its antitumor activities in mice. Remarkably, we observed that the PRL-3 chimeric antibody could efficiently and specifically reduce the formation of PRL-3 expressing metastatic tumors. We further found that natural killer (NK) cells were important in mediating the therapeutic effect, which was only observed in a nude mouse model (T-cell deficient), but not in a Severe Combined Immunodeficiency' (scid ) mouse model (B- and T-cell deficient), indicating the anticancer effect also depends on host B-cell activity. Our study involving 377 nude and scid mice suggest that antibodies targeting intracellular proteins can be developed to treat cancer.
Insights
This study demonstrates that antibodies can target intracellular cancer proteins, like PRL-3, to reduce metastatic tumor formation. The therapeutic effect relies on natural killer (NK) and B-cells, suggesting new antibody strategies for intracellular cancer targets.
Area of Science:
- Immunology
- Oncology
- Molecular Biology
Background:
- Antibodies are highly specific therapeutics but traditionally limited to extracellular targets due to cell entry barriers.
- Many crucial oncogenic proteins are located intracellularly, posing a challenge for antibody-based cancer therapies.
- Developing antibodies against intracellular targets could expand therapeutic options for various cancers.
Purpose of the Study:
- To investigate the potential of chimeric antibodies targeting intracellular oncoproteins for cancer therapy.
- To assess the antitumor efficacy of a novel antibody against the intracellular PRL-3 oncoprotein.
- To elucidate the immune mechanisms, including natural killer (NK) and B-cell activity, involved in antibody-mediated intracellular targeting.
Main Methods:
- Generation of a chimeric antibody specifically targeting the intracellular PRL-3 oncoprotein.
- Assessment of antitumor activity in mouse models, specifically nude (T-cell deficient) and severe combined immunodeficiency (scid, B- and T-cell deficient) mice.
- Evaluation of the role of natural killer (NK) cells and host B-cell activity in mediating therapeutic effects.
Main Results:
- The PRL-3 chimeric antibody demonstrated efficient and specific reduction of PRL-3 expressing metastatic tumors in mice.
- The therapeutic effect was dependent on the presence of natural killer (NK) cells and host B-cell activity.
- Therapeutic efficacy was observed in nude mice but not in scid mice, highlighting the importance of specific immune components.
Conclusions:
- Antibodies can be engineered to effectively target intracellular oncoproteins, expanding the scope of antibody-based cancer therapies.
- The study highlights the critical role of NK cells and B-cells in mediating the antitumor effects of antibodies against intracellular targets.
- This research provides a foundation for developing novel antibody therapies for cancers driven by intracellular oncogenic proteins.
