Abstract
Docetaxel (DOC) is used for the first-line treatment of castration resistant prostate cancer (CPRC). However, the therapeutic effects are limited, only about one half of patients respond to the therapy and severe side effects possibly lead to discontinuation of treatment. Therefore, actual research is focused on the development of new DOC-based combination treatments.In this study we investigated the antitumor effects of a recombinant immunotoxin targeting the prostate specific membrane antigen (PSMA) in combination with DOC in vitro and in vivo. The immunotoxin consists of an anti-PSMA single chain antibody fragment (scFv) as binding and a truncated form of Pseudomonas aeruginosa Exotoxin A (PE40) as toxin domain. The immunotoxin induced apoptosis and specifically reduced the viability of androgen-dependent LNCaP and androgen-independent C4-2 prostate cancer cells. A synergistic cytotoxic activity was observed in combination with DOC with IC50 values in the low picomolar or even femtomolar range. Moreover, combination treatment resulted in an enhanced antitumor activity in a C4-2 SCID mouse xenograft model. This highlights the immunotoxin as a promising therapeutic agent for a future DOC-based combination therapy of CPRC.
Highlights
Prostate cancer remains the most common cancer and the second most leading cause of cancer deaths in industrial countries [1]
We describe the preclinical evaluation of a recombinant immunotoxin targeting the prostate specific membrane antigen (PSMA) in combination with DOC
In this work we have shown that our immunotoxin D7(VL-VH)-PE40 is able to kill PSMA expressing androgen-dependent and –independent prostate cancer cells
Summary
Prostate cancer remains the most common cancer and the second most leading cause of cancer deaths in industrial countries [1]. Several months after beginning ADT leads to an aggressive, androgen-independent grow of tumors cells and virtually all patients show tumor progression [3]. This stage is defined as castration resistant prostate cancer (CRPC). DOC can provoke severe side effects and treatment has possibly to be discontinued because of toxicity or disease progression [4, 5]. In a first clinical trial low-dose DOC in combination with dexamethasone led to a reduced hematological toxicity in CPRC patients compared to the DOC standard therapy [11]
Sign-in/Register to view highlights & summary 
Published Version (
Free)
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call