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Open AccessArticle

Anti-PSMA CAR-Engineered NK-92 Cells: An Off-the-Shelf Cell Therapy for Prostate Cancer

1
Veneto Institute of Oncology IOV-IRCCS, 35128 Padua, Italy
2
Department of Medicine, University of Verona, 37134 Verona, Italy
3
Department of Surgery, Oncology and Gastroenterology, University of Padua, 35128 Padua, Italy
*
Authors to whom correspondence should be addressed.
Authors contributed equally to this work.
Co-senior authors.
Cells 2020, 9(6), 1382; https://doi.org/10.3390/cells9061382
Received: 14 May 2020 / Revised: 29 May 2020 / Accepted: 31 May 2020 / Published: 2 June 2020
(This article belongs to the Special Issue New Developments of Natural Killer (NK) Cells in Immunotherapy)
Prostate cancer (PCa) has become the most common cancer among males in Europe and the USA. Adoptive immunotherapy appears a promising strategy to control the advanced stages of the disease by specifically targeting the tumor, in particular through chimeric antigen receptor T (CAR-T) cell therapy. Despite the advancements of CAR-T technology in the treatment of hematological malignancies, solid tumors still represent a challenge. To overcome current limits, other cellular effectors than T lymphocytes are under study as possible candidates for CAR-engineered cancer immunotherapy. A novel approach involves the NK-92 cell line, which mediates strong cytotoxic responses against a variety of tumor cells but has no effect on non-malignant healthy counterparts. Here, we report a novel therapeutic approach against PCa based on engineering of NK-92 cells with a CAR recognizing the human prostate-specific membrane antigen (PSMA), which is overexpressed in prostatic neoplastic cells. More importantly, the potential utility of NK-92/CAR cells to treat PCa has not yet been explored. Upon CAR transduction, NK-92/CAR cells acquired high and specific lytic activity against PSMA-expressing prostate cancer cells in vitro, and also underwent degranulation and produced high levels of IFN-γ in response to antigen recognition. Lethal irradiation of the effectors, a safety measure requested for the clinical application of retargeted NK-92 cells, fully abrogated replication but did not impact on phenotype and short-term functionality. PSMA-specific recognition and antitumor activity were retained in vivo, as adoptive transfer of irradiated NK-92/CAR cells in prostate cancer-bearing mice restrained tumor growth and improved survival. Anti-PSMA CAR-modified NK-92 cells represent a universal, off-the-shelf, renewable, and cost-effective product endowed with relevant potentialities as a therapeutic approach for PCa immunotherapy. View Full-Text
Keywords: cancer immunotherapy; prostate cancer; CAR; PSMA; NK-92 cell line cancer immunotherapy; prostate cancer; CAR; PSMA; NK-92 cell line
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MDPI and ACS Style

Montagner, I.M.; Penna, A.; Fracasso, G.; Carpanese, D.; Dalla Pietà, A.; Barbieri, V.; Zuccolotto, G.; Rosato, A. Anti-PSMA CAR-Engineered NK-92 Cells: An Off-the-Shelf Cell Therapy for Prostate Cancer. Cells 2020, 9, 1382. https://doi.org/10.3390/cells9061382

AMA Style

Montagner IM, Penna A, Fracasso G, Carpanese D, Dalla Pietà A, Barbieri V, Zuccolotto G, Rosato A. Anti-PSMA CAR-Engineered NK-92 Cells: An Off-the-Shelf Cell Therapy for Prostate Cancer. Cells. 2020; 9(6):1382. https://doi.org/10.3390/cells9061382

Chicago/Turabian Style

Montagner, Isabella M.; Penna, Alessandro; Fracasso, Giulio; Carpanese, Debora; Dalla Pietà, Anna; Barbieri, Vito; Zuccolotto, Gaia; Rosato, Antonio. 2020. "Anti-PSMA CAR-Engineered NK-92 Cells: An Off-the-Shelf Cell Therapy for Prostate Cancer" Cells 9, no. 6: 1382. https://doi.org/10.3390/cells9061382

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