Anti-tax interacting protein-1 (TIP-1) monoclonal antibody targets human cancers

Hong, Yan; Kapoor, Vaishali; Nguyen, Kim Phi Phung; Akers, Walter J.; Li, Hua; Scott, Jalen; Laforest, Richard; Rogers, Buck E.; Thotala, Dinesh; Hallahan, Dennis E.

doi:10.18632/oncotarget.9713

Cited by 11 publications

(15 citation statements)

References 29 publications

(36 reference statements)

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“…Flow cytometry was performed as described earlier [36]. Cells were either sham irradiated or irradiated with 3Gy and harvested at 24, 48, 72 and 96 h. Monoclonal antibodies against human TAF15 and isotype control were purchased from Abcam, USA.…”

Section: Flowcytometrymentioning

confidence: 99%

TAF15 contributes to the radiation-inducible stress response in cancer

et al. 2020

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Resistance to radiation therapy is a significant problem in the treatment of nonsmall cell lung cancer (NSCLC). There is an unmet need to discover new molecular targets for drug development in combination with standard of care cancer therapy. We found that TAF15 was radiation-inducible using phage-displayed peptide libraries. In this study, we report that overexpression of TAF15 is correlated with worsened survival in NSCLC patients. Radiation treatment led to surface induction of TAF15 in vitro and in vivo. We genetically silenced TAF15 which led to a significant reduction in proliferation of NSCLC cells. Cells depleted of TAF15 exhibited cell cycle arrest and enhanced apoptosis through activation and accumulation of p53. In combination with radiation, TAF15 knockdown led to a significant reduction in the surviving fraction of NSCLC cell lines. To determine the importance of TAF15 surface expression, we targeted TAF15 with an antibody. In combination with radiation, the anti-TAF15 antibody led to a reduction in the surviving fraction of cancer cells. These studies show that TAF15 is a radiation-inducible molecular target that is accessible to anticancer antibodies and enhances cell viability in response to radiation.

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Section: Flowcytometrymentioning

confidence: 99%

TAF15 contributes to the radiation-inducible stress response in cancer

et al. 2020

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“…These radiation inducible genes may also serve as antigens for antibody targeted therapy. Yan et al has developed a monoclonal antibody, 2C6F3, that recognizes radiation inducible Tax interacting protein-1 (TIP-1) (30). Binding of 2C6F3 to irradiated cancer cells promoted antibody dependent cell-mediated cytotoxicity and phagocytosis and a radiolabeled 2C6F3 inhibited tumor growth in vivo .…”

Section: Radiation Modulates the Priming Of Adaptive Immune Response mentioning

confidence: 99%

The intersection of radiotherapy and immunotherapy: Mechanisms and clinical implications

2016

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By inducing DNA damage, radiotherapy both reduces tumor burden and enhances anti-tumor immunity. Here, we will review the mechanisms by which radiation induces anti-tumor immune responses that can be augmented using immunotherapies to facilitate tumor regression. Radiotherapy increases inflammation in tumors by activating the NF-κB and the Type I interferon response pathways to induce expression of pro-inflammatory cytokines. This inflammation coupled with antigen release from irradiated cells facilitates dendritic cell maturation and cross-presentation of tumor antigens to prime tumor-specific T cell responses. Radiation also sensitizes tumors to these T cell responses by enhancing T cell infiltration into tumors and the recognition of both malignant cancer cells and non-malignant stroma that present cognate antigen. Yet, these anti-tumor immune responses may be blunted by several mechanisms including regulatory T cells and checkpoint molecules that promote T cell tolerance and exhaustion. Consequently, the combination of immunotherapy using vaccines and/or checkpoint inhibitors with radiation is demonstrating early clinical potential. Overall, this review will provide a global view for how radiation and the immune system converge to target cancers and the early attempts to exploit this synergy in clinical practice.

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“…TIP1 was initially identified as one of the binding partners of the T-cell leukemia viral oncoprotein Tax [9]. A single PSD-95/DlgA/ZO-1 (PDZ) domain (89 amino acids) is the only structural and functional unit in the small protein (total of 124 amino acids in human and mouse), distinguishing TIP-1 from other PDZ proteins [9,10]. The TIP1 expression is elevated in various cancers including lung, breast, and gliomas.…”

Section: Introductionmentioning

confidence: 99%

“…The TIP1 expression is elevated in various cancers including lung, breast, and gliomas. Radiation stress leads to induction of TIP1 within the cells, as well as the cell surface [7,10]. Cell-surface TIP1 is detected on many types of cancer cells in vivo and is not usually present on normal cells [7,10].…”

Section: Introductionmentioning

confidence: 99%

PEGylated peptide to TIP1 is a novel targeting agent that binds specifically to various cancers in vivo

Kapoor

Singh

Rogers

et al. 2019

Journal of Controlled Release

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Targeted molecular imaging allows specific visualization and monitoring of tumors. Cancerspecific peptides have been developed for imaging and therapy. Peptides that specifically target cancer have several advantages including, ease of synthesis, low antigenicity, and enhanced diffusion into tissues. We developed the HVGGSSV peptide as a molecular targeting/imaging agent. HVGGSSV targets Tax interacting protein 1 (TIP1) which is a 14kDa PDZ domaincontaining protein that is overexpressed in cancer. We docked HVGGSSV in silico using the threedimensional structure of TIP1 and found the binding energy was −6.0 kCal/mol. The binding affinity of HVGGSSV to TIP1 protein was found to have a K D of 3.3 × 10 −6 M using surface plasmon resonance. We conjugated a 40kDa PEG to HVGGSSV to enhance the circulation and evaluated the tumor binding in nude mice bearing heterotopic cervical (HT3), esophageal (OE33), pancreatic (BXPC3), lung (A549) and glioma (D54) tumors. NanoSPECT/CT imaging of the mice was performed 48 h and 72 h after injecting with 111 Indium (111 In) labeled PEG-HVGGSSV or PEG-control peptide. SPECT imaging revealed that 111 In-PEG-HVGGSSV specifically bound to cervical, esophageal, pancreatic, lung and brain tumors. Post SPECT biodistribution data further validated tumor-specific binding. Overall, HVGGSSV peptide specifically binds to the major groove of the TIP1 protein surface. PEGylated-HVGGSSV could be used to target cancers that overexpress TIP1.

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Anti-tax interacting protein-1 (TIP-1) monoclonal antibody targets human cancers

Cited by 11 publications

References 29 publications

TAF15 contributes to the radiation-inducible stress response in cancer

TAF15 contributes to the radiation-inducible stress response in cancer

The intersection of radiotherapy and immunotherapy: Mechanisms and clinical implications

PEGylated peptide to TIP1 is a novel targeting agent that binds specifically to various cancers in vivo

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