Integrins: Integrating the Biology and Therapy of Cell–cell Interactions

Targeting the complexity of Src signalling in the tumour microenvironment of pancreatic cancer: from mechanism to therapy

“…Cilengitide was shown to have antitumour activity in recurrent and newly diagnosed glioblastoma [229][230][231][232]; however, further phase III studies showed no significant differences in median overall survival [231], with similar negative findings in PDAC when examined in all-comers [233]. Clinical trials of further integrin antagonists, including intetumumab, volociximab, ATN-161 (Ac-PHSCN-NH2 peptide), abituzumab and etaracizumab, all of which are antibodies or peptide mimetics, have largely yielded no improvements in patient progression-free or overall survival (Table 2) [235,236]; however, specific studies in colon cancer suggest that their antitumour activity may be linked to the presence of a biomarker [237], and, alternatively, may specifically inhibit the progression of bone-associated metastases in prostate cancer [238]. Clinical trials of further integrin antagonists, including intetumumab, volociximab, ATN-161 (Ac-PHSCN-NH2 peptide), abituzumab and etaracizumab, all of which are antibodies or peptide mimetics, have largely yielded no improvements in patient progression-free or overall survival (Table 2) [235,236]; however, specific studies in colon cancer suggest that their antitumour activity may be linked to the presence of a biomarker [237], and, alternatively, may specifically inhibit the progression of bone-associated metastases in prostate cancer [238].…”

“…In contrast, results from a phase I study suggest promising early signals of activity with cilengitide and chemoradiotherapy combination in advanced nonsmall cell lung cancer [234]. Clinical trials of further integrin antagonists, including intetumumab, volociximab, ATN-161 (Ac-PHSCN-NH2 peptide), abituzumab and etaracizumab, all of which are antibodies or peptide mimetics, have largely yielded no improvements in patient progression-free or overall survival (Table 2) [235,236]; however, specific studies in colon cancer suggest that their antitumour activity may be linked to the presence of a biomarker [237], and, alternatively, may specifically inhibit the progression of bone-associated metastases in prostate cancer [238]. Adding to the complexity, anti-integrin compounds may increase intratumoural hypoxia, leading to increased tumour growth, metastasis and chemoresistance in certain settings [239,240], process that is dose-and/or tumour type-dependent [65,241].…”

Peritransplant VLA-4 blockade inhibits endogenous memory CD8 T cell infiltration into high-risk cardiac allografts and CTLA-4Ig resistant rejection

“…[15][16][17][18][19][20] Studies from this and other laboratories have indicated the efficacy of anti-Lymphocyte Function Associated Antigen-1 (LFA-1) antibodies in inhibiting the infiltration of alloantigen-primed T cells, macrophages, and neutrophils into allografts and prolonging allograft survival. [15][16][17][18][19][20] Studies from this and other laboratories have indicated the efficacy of anti-Lymphocyte Function Associated Antigen-1 (LFA-1) antibodies in inhibiting the infiltration of alloantigen-primed T cells, macrophages, and neutrophils into allografts and prolonging allograft survival.…”

“…Leukocyte infiltration into tissue sites of inflammation can be effectively inhibited by antibodies that block the function of molecules required for leukocyte arrest on vascular endothelial cells and infiltration into the parenchymal tissue. [15][16][17][18][19][20] Studies from this and other laboratories have indicated the efficacy of anti-Lymphocyte Function Associated Antigen-1 (LFA-1) antibodies in inhibiting the infiltration of alloantigen-primed T cells, macrophages, and neutrophils into allografts and prolonging allograft survival. [21][22][23][24][25] LFA-1 is also required for assembly of the supramolecular activation complex during T cell receptor mediated activation so anti-LFA-1 mAb is also an effective inhibitor of de novo priming of naïve donor-reactive T cells.…”

Early Events in Japanese Encephalitis Virus Infection: Viral Entry

“…Integrins are a family of cell surface receptors, each composed of two subunits (α and β), that act as linkers between the extracellular matrix and the actin cytoskeleton, and play a critical role in the activation and homing of hematopoietic cells [ 352 ]. Biochemical and molecular studies have demonstrated that in monkey kidney-derived Vero or human cervical carcinoma HeLa cells, the lineage-2 Sarafend strain of WNV binds to α v β 3 integrin, and WNV infection is notably decreased by pretreatment with anti-α v β 3 antibodies, competition with recombinant α v or β 3 protein, or siRNA knockdown of the β 3 subunit; however, somewhat unexpectedly, WNV infection is only marginally affected by pretreatment with synthetic RGD peptides, an inhibitor of integrin-ligand interactions [ 288 , 353 ].…”