Advertisement

Topics

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.

Affiliation

Stem Cell & Molecular Biology Laboratory, Department of Biotechnology, Indian Institute of Technology Madras, Chennai 600036, India.

Journal Details

This article was published in the following journal.

Name: Journal of biotechnology
ISSN: 1873-4863
Pages: 147-55

Links

DeepDyve research library

PubMed Articles [11564 Associated PubMed Articles listed on BioPortfolio]

Murine Retrovirally-Transduced Bone Marrow Engraftment Models of MLL-Fusion-Driven Acute Myelogenous Leukemias (AML).

MLL-rearranged leukemia represents approximately 5% to 10% of adult acute myelogenous leukemia (AML) and nearly half of all infant/pediatric acute leukemia cases. These leukemias have a poor prognosis...

The Efficacy of Generic Imatinib as First- and Second-line Therapy: 3-Year Follow-up of Patients With Chronic Myeloid Leukemia.

Generics of imatinib mesylate, the first tyrosine kinase inhibitor targeting the BCR-ABL1 fusion protein, have recently been approved in many countries as the alternative, low-cost forms for the treat...

Philadelphia chromosome-like acute lymphoblastic leukemia: progress in a new cancer subtype.

Philadelphia chromosome-like (Ph-like) acute lymphoblastic leukemia (ALL) is a newly described, high-risk subtype of B-cell ALL. It is characterized by a gene expression profile similar to that of Ph-...

FISH identifies a KAT6A/CREBBP fusion caused by a cryptic insertional t(8;16) in a case of spontaneously remitting congenital acute myeloid leukemia with a normal karyotype.

Cytogenetics can inform risk stratification in pediatric acute myeloid leukemia (AML). We describe the first case of a newborn with leukemia cutis found to have AML harboring a cryptic insertional t(8...

Toll-like receptor 2 costimulation potentiates the antitumor efficacy of CAR T Cells.

Chimeric antigen receptor (CAR) T-cell immunotherapies have shown unprecedented success in treating leukemia but limited clinical efficacy in solid tumors. Here, we generated 1928zT2 and m28zT2, targe...

Clinical Trials [4651 Associated Clinical Trials listed on BioPortfolio]

Study of DT388GMCSF Fusion Protein in Acute Myelogenous Leukemia (AML) and Chronic Myelomonocytic Leukemia (CMML)

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...

Targeting Leukemic Stem Cell Expressing the IL-1RAP Protein in Chronic Myelogenous Leukemia (CML)

The tyrosine kinase inhibitor therapy (iTKs) is the first-line treatment of chronic myelogenous leukemia (CML). Its effectiveness in controlling the progression of the disease is such tha...

Lymphocytic B-Leukemia (B-CLL) w/Human IL-2 Gene Modified & Human CD40 Ligand-Expressing Autologous Tumor Cells

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.

Phase II Study of the Efficacy and Toxicity of Ontak(Registered Trademark) (Denileukin Diftitox) in the Therapy of Adult T-Cell Leukemia

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...

DTGM Fusion Protein in Treating Patients With Recurrent or Refractory Acute Myeloid Leukemia

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 ...

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.

Quick Search
Advertisement
 


DeepDyve research library

Searches Linking to this Article