scholarly journals Engineering A11 Minibody-Conjugated, Polypeptide-Based Gold Nanoshells for Prostate Stem Cell Antigen (PSCA)–Targeted Photothermal Therapy

2016 ◽  
Vol 22 (1) ◽  
pp. 26-35 ◽  
Author(s):  
Kristine M. Mayle ◽  
Kathryn R. Dern ◽  
Vincent K. Wong ◽  
Kevin Y. Chen ◽  
Shijun Sung ◽  
...  

Currently, there is no curative treatment for advanced metastatic prostate cancer, and options, such as chemotherapy, are often nonspecific, harming healthy cells and resulting in severe side effects. Attaching targeting ligands to agents used in anticancer therapies has been shown to improve efficacy and reduce nonspecific toxicity. Furthermore, the use of triggered therapies can enable spatial and temporal control over the treatment. Here, we combined an engineered prostate cancer–specific targeting ligand, the A11 minibody, with a novel photothermal therapy agent, polypeptide-based gold nanoshells, which generate heat in response to near-infrared light. We show that the A11 minibody strongly binds to the prostate stem cell antigen that is overexpressed on the surface of metastatic prostate cancer cells. Compared to nonconjugated gold nanoshells, our A11 minibody-conjugated gold nanoshell exhibited significant laser-induced, localized killing of prostate cancer cells in vitro. In addition, we improved upon a comprehensive heat transfer mathematical model that was previously developed by our laboratory. By relaxing some of the assumptions of our earlier model, we were able to generate more accurate predictions for this particular study. Our experimental and theoretical results demonstrate the potential of our novel minibody-conjugated gold nanoshells for metastatic prostate cancer therapy.

The Prostate ◽  
2009 ◽  
Vol 69 (13) ◽  
pp. 1422-1434 ◽  
Author(s):  
Frank A. Petrigliano ◽  
Mandeep S. Virk ◽  
Nancy Liu ◽  
Osamu Sugiyama ◽  
Duan Yu ◽  
...  

2017 ◽  
Vol 14 (2) ◽  
pp. 1795-1801 ◽  
Author(s):  
Qiang Zhang ◽  
Guangdong Cheng ◽  
Hongbin Qiu ◽  
Yuexin Wang ◽  
Jingtao Wang ◽  
...  

Author(s):  
Milad Chizari ◽  
Sajad F. Kheshti ◽  
Jaleh Taeb ◽  
Mohammad M. Farajollahi ◽  
Monireh Mohsenzadegan

Background:: Prostate Stem Cell Antigen (PSCA) is a small cell surface protein, overexpressed in 90% of prostate cancers. Determination of epitopes that elicit an appropriate response to the antibody generation is vital for diagnostic and immunotherapeutic purposes for prostate cancer treatment. Presently, bioinformatics B-cell prediction tools can predict the location of epitopes, which is uncomplicated, faster, and more cost-effective than experimental methods. Objective:: We aimed to predict a novel linear peptide for Prostate Stem Cell Antigen (PSCA) protein in order to generate anti-PSCA-peptide (p) antibody and to investigate its effect on prostate cancer cells. Methods:: In the current study, novel linear peptide for PSCA was predicted using in silico methods that utilize a set of linear B-cell epitope prediction tools. Polyclonal antibody (anti-PSCA-p antibody “Patent No. 99318”) against PSCA peptide was generated. The antibody reactivity was determined by the Enzyme-Linked Immunosorbent Assay (ELISA) and its specificity by the Immunocytochemistry (ICC), Immunohistochemistry (IHC), and Western Blotting (WB) assays. The effect of anti-PSCA-p antibody on PSCA-expressing prostate cancer cell line was assessed by Methylthiazolyldiphenyl-Tetrazolium bromide (MTT) assay. Results:: New peptide-fragment of PSCA sequence as “N-CVDDSQDYYVGKKN-C” (PSCA-p) was selected and synthesized. The anti-PSCA-p antibody against the PSCA-p showed immunoreactivity with PSCA-p specifically bound to PC-3 cells. Also, the anti-PSCA-p antibody strongly stained the prostate cancer tissues as compared to Benign Prostatic Hyperplasia (BPH) and normal tissues (P < 0.001). As the degree of malignancy increased, the staining intensity was also elevated in prostate cancer tissue (P < 0.001). Interestingly, anti-PSCA-p antibody showed anti-proliferative effects on PC-3 cells (31%) with no growth inhibition effect on PSCA-negative cells. Conclusion:: In this study, we developed a new peptide sequence (PSCA-p) of PSCA. The PSCA-p targeting by anti-PSCA-p antibody inhibited the proliferation of prostate cancer cells suggesting PSCA-p immunotherapy potential for future prostate cancer studies.


2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Jeremy J. McGuire ◽  
Jeremy S. Frieling ◽  
Chen Hao Lo ◽  
Tao Li ◽  
Ayaz Muhammad ◽  
...  

AbstractBone metastatic prostate cancer (PCa) promotes mesenchymal stem cell (MSC) recruitment and their differentiation into osteoblasts. However, the effects of bone-marrow derived MSCs on PCa cells are less explored. Here, we report MSC-derived interleukin-28 (IL-28) triggers prostate cancer cell apoptosis via IL-28 receptor alpha (IL-28Rα)-STAT1 signaling. However, chronic exposure to MSCs drives the selection of prostate cancer cells that are resistant to IL-28-induced apoptosis and therapeutics such as docetaxel. Further, MSC-selected/IL-28-resistant prostate cancer cells grow at accelerated rates in bone. Acquired resistance to apoptosis is PCa cell intrinsic, and is associated with a shift in IL-28Rα signaling via STAT1 to STAT3. Notably, STAT3 ablation or inhibition impairs MSC-selected prostate cancer cell growth and survival. Thus, bone marrow MSCs drive the emergence of therapy-resistant bone metastatic prostate cancer yet this can be disabled by targeting STAT3.


Oncotarget ◽  
2017 ◽  
Vol 8 (58) ◽  
pp. 98598-98608 ◽  
Author(s):  
Feng Li ◽  
Olga V. Glinskii ◽  
Brian P. Mooney ◽  
Kate Rittenhouse-Olson ◽  
Kenneth J. Pienta ◽  
...  

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