LFA-1 on Leukemic Cells as a Target for Therapy or Drug Delivery

Abstract

Leukemia therapeutics are aiming for improved efficacy by targeting molecular markers differentially expressed on cancerous cells. Lymphocyte function-associated antigen-1 (LFA-1) expression on various types of leukemia has been well studied. Here, the role and expression of LFA-1 on leukemic cells and the possibility of using this integrin as a target for drug delivery is reviewed. To support this rationale, experimental results were also included where cIBR, a cyclic peptide derived from a binding site of LFA-1, was conjugated to the surface of polymeric nanoparticles and used as a targeting ligand. These studies revealed a correlation of LFA-1 expression level on leukemic cell lines and binding and internalization of cIBR-NPs suggesting a differential binding and internalization of cIBR-NPs to leukemic cells overexpressing LFA-1. Nanoparticles conjugated with a cyclic peptide against an accessible molecular marker of disease hold promise as a selective drug delivery system for leukemia treatment.

Epigenetic drug combination overcomes osteoblast-induced chemoprotection in pediatric acute lymphoid leukemia

“…Further investigation is required so that this combination could be better utilized in the clinic for pediatric ALL. Cell adhesion molecules like VLA-4 (Integrin α 4 β 1 ), VLA-5 (Integrin α 5 β 1 ), LFA-1 (Integrin α L β 2 ), and p11 (S100A10) are known to mediate ALL cell binding to osteoblasts and induce chemoprotective effects [8, 24-28]. Given our data supporting the requirement of direct contact between osteoblasts and ALL cells (Fig.…”

Eviction from the sanctuary: Development of targeted therapy against cell adhesion molecules in acute lymphoblastic leukemia

“…Integrin α L β 2 or LFA-1 (leukocyte function-associated antigen-1) is another key heterodimer expressed on the surface of T-ALL cells that confers chemotherapy resistance (24) (Table 3). Multiple myeloma cells co-cultured with bone stromal cells were successfully sensitized to chemotherapy treatments via the use of monoclonal antibodies or an LFA-1 inhibitor (LFA703) (25) (Table 5).…”

Genomic and transcriptomic profiles and in vitro resistance to mitoxantrone and idarubicin in pediatric acute leukemias

“…Overexpression of β2 integrins in T cells allows them to avoid the process of apoptosis induced by FAS protein. According to Phongpradist et al the inhibition of the expression of integrin LFA‐1, which is overexpressed in leukemic cells, results in better treatment outcomes. β2 integrin overexpression is observed in breast adenocarcinoma and melanoma tumors .…”