Nanobodies Targeting Prostate-Specific Membrane Antigen for the Imaging and Therapy of Prostate Cancer

Rosenfeld, Lior; Sananes, Amiram; Zur, Yuval; Cohen, Shira; Dhara, Kalyan; Gelkop, Sigal; Zeev, Efrat Ben; Shahar, Amit; Lobel, Leslie; Akabayov, Barak; Arbely, Eyal; Papo, Niv

doi:10.1021/acs.jmedchem.0c00418

Cited by 30 publications

(21 citation statements)

References 88 publications

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“…PSA-targeted nanocomposites have also shown high levels of activity in imaging-synergized cancer treatment, typically such as FI-mediated chemotherapy 209 or PDT 210 , PET-mediated chemotherapy 211 , MRI/NIR FI-induced hyperthermia 212 , ultrasound-guided gene therapy 213 or chemotherapy 214 , and MRI-induced combination therapy 215 . Furthermore, some PSA-targeted nanoDDS, particularly DTX-derived nanotheranostics, have already hinted valuable prospects in the clinical potential development 216 , phase I 217 , phase II and further clinical stages 218 .…”

Section: Protease-responsive Nanodds For the Targeted Theranostics Of Malignancymentioning

confidence: 99%

Protease-triggered bioresponsive drug delivery for the targeted theranostics of malignancy

Zhang

Guo

et al. 2021

Acta Pharmaceutica Sinica B

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Proteases have a fundamental role in maintaining physiological homeostasis, but their dysregulation results in severe activity imbalance and pathological conditions, including cancer onset, progression, invasion, and metastasis. This striking importance plus superior biological recognition and catalytic performance of proteases, combining with the excellent physicochemical characteristics of nanomaterials, results in enzyme-activated nano-drug delivery systems (nanoDDS) that perform theranostic functions in highly specific response to the tumor phenotype stimulus. In the tutorial review, the key advances of protease-responsive nanoDDS in the specific diagnosis and targeted treatment for malignancies are emphatically classified according to the effector biomolecule types, on the premise of summarizing the structure and function of each protease. Subsequently, the incomplete matching and recognition between enzyme and substrate, structural design complexity, volume production, and toxicological issues related to the nanocomposites are highlighted to clarify the direction of efforts in nanotheranostics. This will facilitate the promotion of nanotechnology in the management of malignant tumors.

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Section: Protease-responsive Nanodds For the Targeted Theranostics Of Malignancymentioning

confidence: 99%

Protease-triggered bioresponsive drug delivery for the targeted theranostics of malignancy

Zhang

Guo

et al. 2021

Acta Pharmaceutica Sinica B

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“…In prostate cancer, PSMA is overexpressed, which is related to castration-resistant prostate and decreased androgen-receptor expression as well as a poor prognosis [27,30]. Evazalipour et al (2014) evaluated the tumor targeting of radiolabeled PSMA Nbs in LNCaP (PSMA+)-and PC3 (PSMA−)-xenografted mice using SPECT/Micro-CT [27].…”

Section: Molecular Imagingmentioning

confidence: 99%

“…Tumor growth inhibition at a low dosage [30] CD38-CAR T-cells Specific and efficient lyses of CD38+ MM cell lines and inhibition of tumor growth [76] TGF-β3 sdAbs Neutralize TGF-β3 and block the TGF-β3-receptor interaction [79] CXCR7 Nbs Inhibition of tumor growth [80] Nb16 and Nb16 Decreases melanoma growth and prolongs survival time. Increases T-cell proliferation and IFN-γ production.…”

Section: Nanobody and Conjugates Effects Referencementioning

confidence: 99%

“…Previously, Talelli et al (2013) encapsulated doxorubicin in EGa1 Nb polymeric-micelles and demonstrated that doxorubicin-EGa1-Nb polymeric-micelles more effectively inhibited tumor growth ( Table 3 ) than EGa1-Nb polymeric-micelles [ 63 ]. More recently, Rosenfeld et al (2020) isolated anti-PSMA Nbs and conjugated an anti-PSMA Nb (NB7) to doxorubicin [ 30 ]. The NB7-doxorubicin conjugate was shown to accumulate in PSMA+ tumors and specifically internalize in PSMA+ cells, leading to doxorubicin-induced cytotoxic activity ( Table 3 ) [ 30 ].…”

Section: Antibodies Versus Nanobodies In Oncology Practicesmentioning

confidence: 99%

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Nanobodies Enhancing Cancer Visualization, Diagnosis and Therapeutics

Naidoo

Chuturgoon

2021

IJMS

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Worldwide, cancer is a serious health concern due to the increasing rates of incidence and mortality. Conventional cancer imaging, diagnosis and treatment practices continue to substantially contribute to the fight against cancer. However, these practices do have some risks, adverse effects and limitations, which can affect patient outcomes. Although antibodies have been developed, successfully used and proven beneficial in various oncology practices, the use of antibodies also comes with certain challenges and limitations (large in size, poor tumor penetration, high immunogenicity and a long half-life). Therefore, it is vital to develop new ways to visualize, diagnose and treat cancer. Nanobodies are novel antigen-binding fragments that possess many advantageous properties (small in size, low immunogenicity and a short half-life). Thus, the use of nanobodies in cancer practices may overcome the challenges experienced with using traditional antibodies. In this review, we discuss (1) the challenges with antibody usage and the superior qualities of nanobodies; (2) the use of antibodies and nanobodies in cancer imaging, diagnosis, drug delivery and therapy (surgery, radiotherapy, chemotherapy and immunotherapy); and (3) the potential improvements in oncology practices due to the use of nanobodies as compared to antibodies.

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“…PSMA can also be engineered into T cells as a reporter for imaging or targeted killing 4,5 . Those attributes have made PSMA a highly leveraged marker for imaging and targeted therapy of PSMA-expressing tumors [6][7][8][9] or cellbased therapies equipped with PSMA as a reporter 10 .…”

Section: Introductionmentioning

confidence: 99%

A prostate-specific membrane antigen (PSMA)-targeted prodrug with a favorable in vivo toxicity profile

Srikanth

Ahn

Cheng

et al. 2020

Preprint

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Prostate-specific membrane antigen (PSMA) is a promising target for the treatment of advanced prostate cancer (PC) and various solid tumors. Although PSMA-targeted radiopharmaceutical therapy (RPT) has enabled significant imaging and prostate-specific antigen (PSA) responses, accumulating clinical data are beginning to reveal certain limitations, including a subgroup of non-responders, relapse, radiation-induced toxicity, and the need for specialized facilities for its administration. To date non-radioactive attempts to leverage PSMA to treat PC with antibodies, nanomedicines or cell-based therapies have met with modest success. We developed a non-radioactive prodrug, SBPD-1, composed of a small-molecule PSMA-targeting moiety, a cancer-selective cleavable linker, and the microtubule inhibitor monomethyl auristatin E (MMAE). SBPD-1 demonstrated high binding affinity to PSMA (Ki = 8.84 nM) and selective cytotoxicity to PSMA-expressing PC cell lines (IC50 = 3.90 nM). SBPD-1 demonstrated a significant survival benefit in two murine models of human PC relative to controls. The highest dose tested did not induce toxicity in immunocompetent mice. The high specific targeting ability of SBPD-1 to PSMA-expressing tumors and its favorable toxicity profile warrant its further development.

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Nanobodies Targeting Prostate-Specific Membrane Antigen for the Imaging and Therapy of Prostate Cancer

Cited by 30 publications

References 88 publications

Protease-triggered bioresponsive drug delivery for the targeted theranostics of malignancy

Protease-triggered bioresponsive drug delivery for the targeted theranostics of malignancy

Nanobodies Enhancing Cancer Visualization, Diagnosis and Therapeutics

A prostate-specific membrane antigen (PSMA)-targeted prodrug with a favorable in vivo toxicity profile

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