Valerie R. Wiersma

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PURPOSE Adoptive T-cell therapy generally fails to induce meaningful anticancer responses in patients with solid tumors. Here, we present a novel strategy designed to selectively enhance the tumoricidal activity of T cells by targeted delivery of TNF-related apoptosis-inducing ligand (TRAIL) to the T-cell surface. EXPERIMENTAL DESIGN We constructed two(More)
Antibodies that block PD-L1/PD-1 immune checkpoints restore the activity of functionally-impaired antitumor T cells. These antibodies show unprecedented clinical benefit in various advanced cancers, particularly in melanoma. However, only a subset of cancer patients responds to current PD-L1/PD-1-blocking strategies, highlighting the need for further(More)
Background:In certain cancers, expression of CXCL16 and its receptor CXCR6 associate with lymphocyte infiltration, possibly aiding anti-tumour immune response. In other cancers, CXCL16 and CXCR6 associate with pro-metastatic activity. In the current study, we aimed to characterise the role of CXCL16, sCXCL16, and CXCR6 in ovarian cancer(More)
Since their discovery, antibodies have been viewed as ideal candidates or "magic bullets" for use in targeted therapy in the fields of cancer, autoimmunity, and chronic inflammatory disorders. A wave of antibody-dedicated research followed, which resulted in the clinical approval of a first generation of monoclonal antibodies for cancer therapy such as(More)
The expedient removal of dying, damaged or altered cells by phagocytosis is essential for homeostasis. However, cancer cells can evade such phagocytic elimination by cell surfaceupregulation of phagocyte-inhibitory signals, such as CD47. CD47 is a prominent ‘don’t eat me’ signal that binds to signalregulatory protein alpha (SIRPa/SIRPA) expressed on(More)
ACKNOWLEDGMENTS We thank Shin-ichi Nishikawa, Takahiro Kunisada, and Vince Hearing for the antibodies. We are grateful to the reviewers of the manuscript for providing additional ideas that we have included. This work was funded by the NH&MRC of Australia and the Cancer Council of Queensland. GJW is the recipient of a Senior Research Fellowship from the(More)
Calreticulin is a pleiotropic molecule that normally resides in the lumen of the endoplasmic reticulum (ER). Here, it has various functions, ranging from regulation of calcium homeostasis to ensuring proper protein folding. More recently, calreticulin gained special interest for its extracellular functions, where it has direct immunomodulatory activity. In(More)
The therapeutic effect of anti-cancer monoclonal antibodies stems from their capacity to opsonize targeted cancer cells with subsequent phagocytic removal, induction of antibody-dependent cell-mediated cytotoxicity (ADCC) or induction of complement-mediated cytotoxicity (CDC). The major immune effector cells involved in these processes are natural killer(More)
Recently, a small subset of T cells that expresses the B cell marker CD20 has been identified in healthy volunteers and in patients with rheumatoid arthritis and multiple sclerosis. The origin of these CD20-positive T cells as well as their relevance in human disease remains unclear. Here, we identified that after functional B cell/T cell interaction CD20(More)
In recent years, an important role has emerged for the glycan-binding protein Galectin-9 (Gal-9) in health and disease. In normal physiology, Gal-9 seems to be a pivotal modulator of T-cell immunity by inducing apoptosis in specific T-cell subpopulations. Because these T-cell populations are associated with autoimmunity, inflammatory disease, and graft(More)