AI Article Synopsis
- Researchers developed humanized immunotoxins targeting the prostate-specific membrane antigen (PSMA) to treat prostate cancer.
- The immunotoxins combined a humanized antibody fragment with toxic components from Pseudomonas aeruginosa, which were then tested for their ability to kill cancer cells.
- Results showed that these immunotoxins effectively bound to PSMA and demonstrated high cytotoxicity against prostate cancer cells, suggesting potential for clinical use.
Article Abstract
Background: We generated humanized/de-immunized immunotoxins targeting the prostate-specific membrane antigen (PSMA) and tested their cytotoxic activity against prostate cancer cells in vitro.
Materials And Methods: The humanized/de-immunized version of our murine anti-PSMA single-chain antibody fragment (scFv) D7, termed hD7-1(VL-VH), was ligated to the 40-kDa toxin domain of Pseudomonas aeruginosa exotoxin A (PE40), and to the deimmunized 24-kDa toxin domains PE24 or PE24mut. The immunotoxins designated as hD7-1(VL-VH)-PE40, hD7-1(VL-VH)-PE24 and hD7-1(VL-VH)-PE24mut were bacterially expressed and purified by affinity chromatography. Binding and cytotoxicity were examined by flow cytometry and viability assay, respectively.
Results: All immunotoxins revealed strong binding to prostate cancer cells expressing PSMA and specific cytotoxicity, with half-maximal inhibitory concentration values in the picomolar range.
Conclusion: We successfully created powerful anti-PSMA immunotoxins with reduced immunogenicity for further clinical development and application against advanced prostate cancer.
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| http://dx.doi.org/10.21873/anticanres.12192 | DOI Listing |
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