Modified DT-IL2 fusion toxin targeting uniquely IL2Ralpha expressing leukemia cell lines - Construction and characterization.
Summary of "Modified DT-IL2 fusion toxin targeting uniquely IL2Ralpha expressing leukemia cell lines - Construction and characterization."
Immunotoxins are fusion proteins of modified toxin conjugated to tumor cell selective ligand. Denileukin diftitox approved by FDA for treatment of CTCL is diphtheria toxin (DT)/IL2 fusion protein targeted to high affinity IL2R. Here, we have attempted to target the more uniquely expressed low affinity IL2R (IL2Ralpha). We designed four immunotoxins, SPRSV1 was designed to code for a single protein of DT (390) and IL2 (133) without any extra amino acids at the junction. SPRSV2 was designed to selectively target low affinity IL2R, it codes for DT (390) and IL2 (69). We also constructed SPRSV3 encoding for only DT (390) without any ligand, as negative control and SPRSV4 was designed similar to commercial equivalent denileukin diftitox, it codes for DT (387) and IL2 (133) with His at the junction. The cytotoxic activities of these immunotoxins were tested in various cell lines, cell lines lacking IL2R expression and healthy MNC were used as controls. The activities of SPRSV1 and SPRSV2 were comparable to that of SPRSV4. SPRSV2 exhibited potent cytotoxicity effectively targeted to alpha subunit of IL2R on various leukemia cell lines. Our studies also showed a negative correlation between CD25 expression and percentage cell viability after treatment with immunotoxins.
Stem Cell & Molecular Biology Laboratory, Department of Biotechnology, Indian Institute of Technology Madras, Chennai 600036, India.
This article was published in the following journal.
Name: Journal of biotechnology
- PubMed Source: http://www.ncbi.nlm.nih.gov/pubmed/20580754
- DOI: http://dx.doi.org/10.1016/j.jbiotec.2010.04.006
Highly potent biotoxins like Pseudomonas exotoxin A (ETA) are attractive payloads for tumor targeting. However, despite replacement of the natural cell-binding domain of ETA by tumor-selective antibod...
The aim of the present study is to establish a bacterial clone capable of secreting an integrin αvβ3 targeting probe with bioluminescent and fluorescent activities, and to verify its specific target...
Reciprocal chromosomal translocations are observed in one-third of acute myeloid leukemia (AML) cases. Targeting and understanding the effects of the resulting aberrant oncogenic fusion proteins may h...
Relapsed acute lymphoblastic leukemia (ALL) is difficult to treat despite the availability of aggressive therapies. Chimeric antigen receptor-modified T cells targeting CD19 may overcome many limitati...
SIRT1 is an important regulator of cellular stress response and genomic integrity. Its role in tumorigenesis is debated controversially. Whereas SIRT1 can act as a tumor suppressor in some solid tumor...
DTGM belongs to a new generation of drugs designed to target leukemic cells. To achieve this, DTGM takes advantage of the ability of naturally-produced growth factor (GM, granulocyte-macro...
The purpose of this study is to learn the safety and cancer-fighting effects of using IL-2 with the vaccines ("shots") made for you.
Adult T-cell leukemia (ATL) is and aggressive characterized by the presence of CD4/CD25-expressing T cells (interleukin-2 [IL-2]R expressing) in the peripheral blood and in lymphoid and ot...
RATIONALE: DTGM fusion protein may be able to locate cancer cells and stop them from growing. PURPOSE: Phase I/II trial to study the effectiveness of DTGM fusion protein in treating ...
This study uses autologous (one's own) CD4 T cells modified with a viral vector expressing a genetic antisense targeting HIV, this vector is called VRX496. Study treatment is by intraveno...
Medical and Biotech [MESH] Definitions
Translation products of a fusion gene derived from CHROMOSOMAL TRANSLOCATION of C-ABL GENES to the genetic locus of the breakpoint cluster region gene on chromosome 22. The p210(bcr-abl) fusion protein is found in patients with LEUKEMIA, MYELOGENOUS, CHRONIC, BCR-ABL POSITIVE. The p190(bcr-abl) fusion protein is found in patients with PRECURSOR CELL LYMPHOBLASTIC LEUKEMIA-LYMPHOMA. The activation of human c-abl by chromosomal translocation is essentially the same as the activation of murine c-abl by viral translocation in ABELSON MURINE LEUKEMIA VIRUS.
Myeloid-lymphoid leukemia protein is a transcription factor that maintains high levels of HOMEOTIC GENE expression during development. The GENE for myeloid-lymphoid leukemia protein is commonly disrupted in LEUKEMIA and combines with over 40 partner genes to form FUSION ONCOGENE PROTEINS.
A myelodysplastic/myeloproliferative disorder characterized by myelodysplasia associated with bone marrow and peripheral blood patterns similar to CHRONIC MYELOID LEUKEMIA, but cytogenetically lacking a PHILADELPHIA CHROMOSOME or bcr/abl fusion gene (GENES, ABL).
A multifunctional heterogeneous-nuclear ribonucleoprotein that may play a role in homologous DNA pairing and recombination. The N-terminal portion of protein is a potent transcriptional activator, while the C terminus is required for RNA binding. The name FUS refers to the fact that genetic recombination events result in fusion oncogene proteins (ONCOGENE PROTEINS, FUSION) that contain the N-terminal region of this protein. These fusion proteins have been found in myxoid liposarcoma (LIPOSARCOMA, MYXOID) and acute myeloid leukemia.
A toxin produced by certain pathogenic strains of ESCHERICHIA COLI such as ESCHERICHIA COLI O157. It shares 50-60% homology with SHIGA TOXIN and SHIGA TOXIN 1.