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.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6027395 | PMC |
| http://dx.doi.org/10.3390/biomedicines6020072 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Multiple Myeloma Cells Shift the Fate of Cytolytic ILC2s Towards TIGIT-Mediated Cell Death.
Cancers (Basel)
January 2025
Laboratory of Immunology and Biotherapy, Department Human Pathology in Adulthood and Childhood "Gaetano Barresi", University of Messina, 98125 Messina, Italy.
Background: Growing evidence attests to the multifaceted roles of group 2 innate lymphoid cells (ILC2s) in cancer immunity. They exhibit either pro- or anticancer activity depending on tumor type but their function in Multiple Myeloma (MM) is still not elucidated.
Methods: The bone marrow (BM) and peripheral blood (PB) of patients (pts) with MM or precancerous conditions were collected, and specific properties of ILC2 subsets were assessed by flow cytometry.
An immunosenescent CD8+ T cell subset in patients with axial Spondyloarthritis and Psoriatic Arthritis links spontaneous motility to telomere shortening and dysfunction.
Arthritis Rheumatol
January 2025
Department of Biology and Biotechnologies "Charles Darwin", Sapienza University of Rome, Rome, Italy.
Objective: A pathogenetic role of CD8+ T lymphocytes in radiographic axial spondyloarthritis (r-axSpA) and other spondyloarthritis (SpA) is sustained by genome-wide association studies (GWAS) and by the expansion of public T cell clonotypes in the target tissues. This study investigates the migration of CD8+ T cells, along with their phenotype and functions in patients with r-axSpA and psoriatic arthritis (PsA).
Methods: Peripheral blood CD8+ and CD4+ T cells were isolated from r-axSpA (n= 128), PsA (n= 60) and rheumatoid arthritis (RA, n= 74) patients and healthy donors (HD, n= 79).
Polyfunctional CD8CD226RUNX2 effector T cells are diminished in advanced stages of chronic lymphocytic leukemia.
Mol Oncol
January 2025
Division of Foundational Sciences, Mike Petryk School of Dentistry, University of Alberta, Edmonton, Canada.
CD8 T cells, a subset of T cells identified by the surface glycoprotein CD8, particularly those expressing the co-stimulatory molecule CD226, play a crucial role in the immune response to malignancies. However, their role in chronic lymphocytic leukemia (CLL), an immunosuppressive disease, has not yet been explored. We studied 64 CLL patients and 25 age- and sex-matched healthy controls (HCs).
View Article and Find Full Text PDFUTX Epigenetically Imposes a Cytolytic Effector Program in Autoreactive Stem-like CD8+ T cell Progenitors.
bioRxiv
December 2024
Department of Microbiology, Immunology, and Molecular Genetics, UCLA David Geffen School of Medicine; Los Angeles, CA 90095.
Type 1 Diabetes Mellitus (T1D) is an autoimmune disease caused by unremitting immune attack on pancreas insulin-producing beta cells. Persistence of the autoimmune response is mediated by TCF1+ Ly108+ progenitor CD8+ T (T) cells, a stem-like population that gives rise to exhausted effectors with limited cytolytic function in chronic virus infection and cancer. What paradoxically drives T conversion to highly cytolytic effectors in T1D, however, remains unclear.
View Article and Find Full Text PDFInteraction of an Oomycete Nep1-like Cytolysin with Natural and Plant Cell-Mimicking Membranes.
J Membr Biol
December 2024
Department of Molecular Biology and Nanobiotechnology, National Institute of Chemistry, Hajdrihova 19, 1000, Ljubljana, Slovenia.
Article Synopsis
- Plants face attacks from pathogens that use effectors like necrosis- and ethylene-inducing peptide-1-like proteins (NLPs) to invade and damage them.
- NLPs, known for causing cell death and tissue damage, disrupt the plant's plasma membrane through unique mechanisms that create small, temporary membrane ruptures.
- Recent research utilized confocal fluorescence microscopy to analyze how NLP interacts with model plant cell membranes, revealing that NLP's permeabilization effects depend on its concentration and time of exposure, and confirming its binding and structural changes on these membranes.
Want AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!