Related Experiment Video
Updated: Jul 9, 2026
10:23
Evaluation of Caspase Activation to Assess Innate Immune Cell Death
Published on: January 20, 2023
HPV16E7-specific affitoxin induces GSDME-mediated pyroptosis via a caspase-3-independent pathway
Yanheng Li1, Xisha Jing1, Jinhao Liu1
1Department of Pathogen Biology and Immunology, School of Basic Medical Sciences, Wenzhou Medical University, Zhejiang 325032, China.
International Journal of Antimicrobial Agents
|July 7, 2026
Summary
A novel fusion protein, ZHPV16E7-GrB, effectively targets human papillomavirus (HPV) 16-positive cervical cancer cells. This therapy induces GSDME-mediated pyroptosis, a programmed cell death pathway, to suppress tumor growth.
Area of Science:
- Oncology
- Molecular Biology
- Immunology
Background:
- Human papillomavirus (HPV) oncoprotein E7 drives cervical cancer progression in HPV16-positive cells.
- Targeting HPV16E7 is a promising therapeutic strategy for cervical cancer.
Purpose of the Study:
- To develop and characterize a novel affitoxin, ZHPV16E7-GrB, for targeted HPV16-specific cervical cancer therapy.
- To investigate the anti-tumor mechanism of ZHPV16E7-GrB, focusing on pyroptosis induction.
Main Methods:
- Construction of a fusion protein ZHPV16E7-GrB combining a cell-penetrating peptide, an HPV16E7-specific affibody, and human granzyme B.
- Assessment of binding affinity, cellular uptake, and specificity in HPV16-positive cervical cancer cells.
- Analysis of pyroptosis induction markers (GSDME cleavage, cytokine release, LDH release) and caspase-3 independence.
- In vivo evaluation of tumor growth suppression in a TC-1 xenograft mouse model.
Main Results:
- ZHPV16E7-GrB demonstrated specific binding to HPV16E7 and rapid uptake by HPV16-positive cancer cells.
- The fusion protein induced significant pyroptosis, characterized by GSDME cleavage and release of inflammatory cytokines, independent of caspase-3.
- ZHPV16E7-GrB treatment led to substantial tumor growth suppression in vivo.
- GSDME was identified as the key executor of pyroptosis in this caspase-3-independent pathway.
Conclusions:
- ZHPV16E7-GrB represents a novel therapeutic approach for HPV16-specific cervical cancer.
- The study elucidates a new anti-tumor pathway involving GSDME-mediated, caspase-3-independent pyroptosis induced by ZHPV16E7-GrB.
- This provides mechanistic insights for developing targeted therapies against HPV-associated cancers.
Related Concept Videos
01:17The Extrinsic Apoptotic Pathway
The extrinsic apoptotic pathway is initiated when extracellular death-inducing signals, such as specific cytokines, activate the death receptors expressed on the cell surface. The immune cells involved in this pathway are natural killer cells (NK cells) and cytotoxic T-lymphocytes. NK cells are critical in innate immune response, while cytotoxic T-lymphocytes are associated with adaptive immune response. These cells recognize specific receptors expressed on the altered cells and activate...
01:24Caspases
Caspase, a family of cysteine proteases, serve as effectors in apoptosis. The ced3 gene in C.elegans was first identified to be involved in apoptosis. This gene encodes the ced-3 caspase that is similar to the interleukin-1-beta converting enzyme or ICE in mammals. In addition to apoptosis, caspases also function in the inflammatory response. Inflammatory caspases are essential in activating pro-inflammatory cytokines that recruit immune cells and block the replication of pathogens inside cells.
01:31The Intrinsic Apoptotic Pathway
Internal cellular stress, such as cellular injury or hypoxia, triggers intrinsic apoptosis. The B-cell lymphoma 2 (Bcl-2) family of proteins are the primary regulators of the intrinsic apoptotic pathway. For example, during DNA damage, checkpoint proteins, such as Ataxia Telangiectasia Mutated (ATM protein) and Checkpoints Factor-2 (Chk2) proteins, are activated. These proteins phosphorylate p53 which further activates pro-apoptotic proteins, such as Bax, Bak, PUMA, and Noxa, and inhibits...
01:30Apoptosis
Apoptosis is a combination of two Greek words, 'apo' and 'ptosis,' meaning separation and falling off, respectively. Hippocrates used this word to describe gangrene, which was caused due to bandaging of fractured bones. Apoptosis was distinguished from necrosis in 1970 when John Kerr reported observations of morphological changes occurring during apoptosis. During one experiment, he observed that the disruption of blood supply to the liver tissue resulted in a size reduction of the tissue.
01:30Overview of Cell Death
Cell death is an essential process where the body gets rid of old or damaged cells. Cell proliferation and death need to be balanced, as an imbalance between the two may lead to cancer or autoimmune diseases.
Cell death was observed in the early 19th century, but there was no experimental evidence to prove it. In 1842, Carl Vogt first discovered cell death in a metamorphic toad; however, it was not termed ‘cell death.’ Scientists discovered different cell death pathways only in the 20th century...
Cell death was observed in the early 19th century, but there was no experimental evidence to prove it. In 1842, Carl Vogt first discovered cell death in a metamorphic toad; however, it was not termed ‘cell death.’ Scientists discovered different cell death pathways only in the 20th century...