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Updated: Feb 8, 2026

A High Yield and Cost-efficient Expression System of Human Granzymes in Mammalian Cells
Published on: June 10, 2015
Human Granzyme B Based Targeted Cytolytic Fusion Proteins
Precious Hlongwane1, Neelakshi Mungra2, Suresh Madheswaran3
1Medical Biotechnology and Immunotherapy Unit, Institute of Infectious Disease and Molecular Medicine, Faculty of Health Sciences, University of Cape Town, Cape Town 7700, South Africa. hlnpre001@myuct.ac.za.
Abstract:
Cancer immunotherapy aims to selectively target and kill tumor cells whilst limiting the damage to healthy tissues. Controlled delivery of plant, bacterial and human toxins or enzymes has been shown to promote the induction of apoptosis in cancerous cells. The 4th generation of targeted effectors are being designed to be as humanized as possible—a solution to the problem of immunogenicity encountered with existing generations. Granzymes are serine proteases which naturally function in humans as integral cytolytic effectors during the programmed cell death of cancerous and pathogen-infected cells. Secreted predominantly by cytotoxic T lymphocytes and natural killer cells, granzymes function mechanistically by caspase-dependent or caspase-independent pathways. These natural characteristics make granzymes one of the most promising human enzymes for use in the development of fusion protein-based targeted therapeutic strategies for various cancers. In this review, we explore research involving the use of granzymes as cytolytic effectors fused to antibody fragments as selective binding domains.
Insights
Cancer immunotherapy utilizes human granzymes, which are enzymes that induce apoptosis, as targeted effectors. These granzymes are fused to antibody fragments for precise delivery to cancer cells, minimizing damage to healthy tissues.
Area of Science:
- Oncology
- Immunology
- Biotechnology
Background:
- Cancer immunotherapy seeks targeted tumor cell destruction with minimal healthy tissue damage.
- Controlled delivery of toxins and enzymes can induce apoptosis in cancer cells.
- Existing immunotherapies face immunogenicity issues, driving the development of humanized effectors.
Purpose of the Study:
- To review research on using granzymes as cytolytic effectors in cancer therapeutics.
- To explore the fusion of granzymes with antibody fragments for targeted cancer therapy.
Main Methods:
- Review of scientific literature on granzyme-based cancer immunotherapy.
- Analysis of granzyme mechanisms (caspase-dependent/independent pathways).
- Examination of antibody fragment-granzyme fusion protein strategies.
Main Results:
- Granzymes are potent serine proteases naturally involved in programmed cell death.
- Cytotoxic T lymphocytes and natural killer cells secrete granzymes.
- Fusion proteins combine granzyme's killing ability with antibody fragment's targeting specificity.
Conclusions:
- Granzymes are promising human enzymes for targeted cancer therapy development.
- Antibody fragment-granzyme fusions offer a strategy to overcome immunogenicity and enhance selectivity.
- This approach holds potential for novel therapeutic strategies against various cancers.
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