The prostate-specific membrane antigen (PSMA) is expressed in advanced prostate cancer and targeting this protein is used for imaging of advanced prostate cancer as well as development of new targeting strategies. The objective a study by Vincent DiPippo, William Olson, Holly Nguyen, Lisha Brown, Robert Vessella and Eva Corey was designed to evaluate the efficacy of the antibody drug conjugate PSMA ADC against a series of patient-derived prostate cancer xenografts (LuCaP 58, LuCaP 77, LuCaP 96CR, and LuCaP 105) with different characteristics, including varying levels of PSMA expression and responses to androgen suppression.

In this trial, the researchers used mice bearing subcutaneous LuCaP prostate cancer-derived xenografts. The mice received the PSMA antibody monomethyl auristatin E (MMAE) drug conjugate (PSMA ADC) in which the antibody and MMAE are linked via a protease-cleavable linker.

The dose of the PSMA ADC ranged from 1 to 6 mg/kg. Unmodified PSMA mAb + free MMAE at the amount equivalent to those contained in 6 mg/kg PSMA ADC was used as control. All treatments were administered once a week via tail-vein injections and repeated four times once a week and tumor responses were monitored for 10 weeks. To determine PSMA and AR expression and effects on proliferation IHC analyses were performed.

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The treatment responses varied widely across the various number of tumor models and included complete tumor regressions in LuCaP 96CR to largely unimpeded tumor progression of LuCaP 58, which had the lowest baseline level of PSMA expression.

Furthermore, intermediate antitumor effects were seen for LuCaP 77 and LuCaP 105 tumors, despite their having similar basal expression of PSMA as LuCaP 96CR. The researchers also detected substantial differences in responses even within the same model, indicating that PSMA expression is not the only factor involved in treatment outcomes.

These outcomes showed a high efficacy of PSMA ADC in advanced prostate cancer but also considerable variability in effects despite PSMA expression. Based on these results, the researchers concluded that further studies to identify tumor characteristics that are predictive of treatment response are warranted. Some of these studies are ongoing.

Published in: The Prostate