The application of prostate specific membrane antigen in CART‑cell therapy for treatment of prostate carcinoma (Review)

Ullah, Kifayat; Peprah, Frank Addai; Feng, Yue; Shi, Haifeng

doi:10.3892/or.2018.6758

Cited by 4 publications

(5 citation statements)

References 62 publications

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“…PSCA has also become an important target for targeted therapy of PCa. These studies suggest that PCa is a favorable tumor for CAR-T cells therapy ( 65 ).…”

Section: Car-t Cells For Urologic Neoplasmsmentioning

confidence: 99%

CAR-T Cells in the Treatment of Urologic Neoplasms: Present and Future

et al. 2022

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In recent years, with the breakthrough of CAR-T cells in the treatment of hematological tumors, they are increasingly being used to treat solid tumors, including urologic neoplasms. There are many relatively specific targets for urologic neoplasms, especially prostate cancer. Besides, urologic neoplasms tend to progress more slowly than tumors in other organs of the body, providing ample time for CAR-T cell application. Therefore, CAR-T cells technology has inherent advantages in urologic neoplasms. CAR-T cells in the treatment of urologic neoplasms have been extensively studied and preliminary achievements have been made. However, no breakthrough has been made due to the problems of targeting extra-tumor cytotoxicity and poor anti-tumor activity. we systematacially summarized the research actuality of CAR-T cells in urologic neoplasms, discussed the potential value and difficulties of the research. The application of CAR-T cells in the treatment of urologic neoplasms requires improvement of function through screening for better targets, modification of CAR structures, or in combination with other antitumor approaches.

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“…PSCA has also become an important target for targeted therapy of PCa. These studies suggest that PCa is a favorable tumor for CAR-T cells therapy ( 65 ).…”

Section: Car-t Cells For Urologic Neoplasmsmentioning

confidence: 99%

CAR-T Cells in the Treatment of Urologic Neoplasms: Present and Future

et al. 2022

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“…Adoptive immunotherapy appears to be a promising strategy to control the advanced stages of cancer by specific targeting, in particular through chimeric antigen receptor T (CAR T) cell therapy or, more recently, CAR-NK [51][52][53]. The high curative potential against hematologic malignancies afforded by CAR T cells supports the large number of current clinical trials (nine directed against PSMA: 8 as CAR-T and 1 as In particular, the ability of X770-scFvD2B to detect prostate cancer was monitored by fluorescent reflectance imaging (FRI) and by fluorescence molecular tomography (FMT), and the accumulation of the labeled scFvD2B with respect to the labeled control scFv increased 10-fold at 72 h and 20-fold at 96 h.…”

Section: Scfv As a Therapeutic Agentmentioning

confidence: 99%

Section: Scfv As a Therapeutic Agentmentioning

confidence: 99%

Validity of Anti-PSMA ScFvD2B as a Theranostic Tool: A Narrative-Focused Review

et al. 2021

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Prostate cancer (PCa) is the second leading cause of cancer among men, and its diagnosis and adequate staging are fundamental. Among the biomarkers identified in recent years for PCa management, prostate-specific-membrane-antigen (PSMA), physiologically expressed at a low level on healthy prostate and in other normal tissues and highly overexpressed in PCa, represents a reliable marker ideal for imaging and therapy. The development of anti-PSMA antibodies, such as D2B, demonstrated slow clearance of intact antibodies compared with fragments resulting in low tumor-to-blood ratios; however, the modular structural and functional nature of antibodies allowed the generation of smaller fragments, such as scFvs. In this review of the anti-PSMA antibody fragment scFvD2B, we combined further characterization of its biomolecular and tissue cross-reactivity characteristics with a comprehensive summary of what has already been performed in preclinical models to evaluate imaging and therapeutic activities. A molecular dynamics study was performed, and ScFvD2B occupied a limited conformational space, characterized by low-energy conformational basins, confirming the high stability of the protein structure. In the cross-reactivity study, the weak/absent immunoreactivity in non-tumor tissues was comparable to the PSMA expression reported in the literature. Biodistribution studies and therapeutic treatments were conducted in different animal models obtained by subcutaneous or locoregional injection of PSMA-positive-versus-negative xenografts. The maximum tumor uptake was observed for 123I(SPECT), 124I(PET), and optical imaging, which avoids kidney accumulation (compared with radiometals) and leads to an optimal tumor-to-kidney and tumor-to-background ratios. Regarding its possible use in therapy, experimental data suggested a strong and specific antitumor activity, in vitro and in vivo, obtained using CAR-T or NK-92/CAR cells expressing scFvD2B. Based on presented/reviewed data, we consider that scFvD2B, due to its versatility and robustness, seems to: (i) overcome some problems observed in other studied scFvs, very often relatively unstable and prone to form aggregates; (ii) have sufficient tumor-to-background ratios for targeting and imaging PSMA-expressing cancer; (iii) significantly redirect immune killing cells to PSMA-positive tumors when inserted in second-generation CAR-T or NK-92/CAR cells. These data suggest that our product can be considered the right reagent to fill the gap that still exists in PCa diagnosis and treatment.

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“…PCa is a lucrative target for CAR-T cell therapy given the presence of multiple tumor specific antigens such as PAP, PSCA, PSMA, and PSA. 83 CAR-T cells comprise three main parts: an extracellular component that recognizes antigens, a transmembrane part as well as an intracellular component that mediates the final signal transduction. 84 Development in genetic engineering has led to tremendous improvisations in the structure of CAR-T cells, with four generations of CAR-T cells, each new one being a functional upgrade to its predecessor.…”

Section: Pd-1/pd-l Pathwaymentioning

confidence: 99%

“…PCa is a lucrative target for CAR-T cell therapy given the presence of multiple tumor specific antigens such as PAP, PSCA, PSMA, and PSA. 83 …”

Section: Adoptive Cell Therapymentioning

confidence: 99%

Immunotherapy in prostate cancer: current state and future perspectives

Handa¹,

Hans

Goel

et al. 2020

Therapeutic Advances in Urology

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Metastatic castrate resistant prostate cancer (PCa) remains an incurable entity. In the era of immunotherapy, the complex PCa microenvironment poses a unique challenge to the successful application of this class of agents. However, in the last decade, a tremendous effort has been made to explore this field of therapeutics. In this review, the physiology of the cancer immunity cycle is highlighted in the context of the prostate tumor microenvironment, and the current evidence for use of various classes of immunotherapy agents including vaccines (dendritic cell based, viral vector based and DNA/mRNA based), immune checkpoint inhibitors, Chimeric antigen receptor T cell therapy, antibody-mediated radioimmunotherapy, antibody drug conjugates, and bispecific antibodies, is consolidated. Finally, the future directions for combinatorial approaches to combat PCa are discussed.

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The application of prostate specific membrane antigen in CART‑cell therapy for treatment of prostate carcinoma (Review)

Cited by 4 publications

References 62 publications

CAR-T Cells in the Treatment of Urologic Neoplasms: Present and Future

CAR-T Cells in the Treatment of Urologic Neoplasms: Present and Future

Validity of Anti-PSMA ScFvD2B as a Theranostic Tool: A Narrative-Focused Review

Immunotherapy in prostate cancer: current state and future perspectives

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