Vascular Targeted Therapy With Anti–Prostate-Specific Membrane Antigen Monoclonal Antibody J591 in Advanced Solid Tumors

Abstract

Acceptable toxicity and excellent targeting of known sites of metastases were demonstrated in patients with multiple solid tumor types, highlighting a potential role for the anti-PSMA antibody J591 as a vascular-targeting agent.

Folate hydrolase (prostate-specific antigen) 1 expression in bladder cancer subtypes and associated tumor neovasculature

“…8,18,24,25 As an example, antibodies to FH(PSA)1 have been used for in vivo localization and treatment of metastatic prostate cancer 15,16 and have been shown to target the neovasculature endothelium of multiple solid tumor malignancies in humans. 26,27 Review of the literature reveals conflicting results for the expression of FH(PSA)1 in normal urothelium and UCC (Table 6). In normal urothelium, reported FH(PSA)1 expression ranges from ubiquitous (18/18 specimens 6 and 9/9 specimens 9 ) to non-existent (0/846 7 and 0/5 specimens 8 ).…”

High expression of prostate-specific membrane antigen in the tumor-associated neo-vasculature is associated with worse prognosis in squamous cell carcinoma of the oral cavity

“…Two clinical trials have recently established the feasibility of vascular targeting using PSMA-specific antibodies 35,36 and a number of PSMA-targeting molecules ranging from monoclonal antibodies to PSMA-binding ligands, RNA aptamers, targeted nanoparticles and viral PSMA-targeting systems are currently under pre-clinical or clinical investigation in different tumor types. [37][38][39][40][41] Given the strong association of PSMA expression with survival it remains to be shown if a PSMA-specific targeting approach would show a therapeutic benefit in a subset of patients with oral squamous cell carcinoma.…”

Prostate-specific membrane antigen expression in regeneration and repair

“…J591 is a humanized monoclonal antibody to PSMA, which is currently being evaluated in clinical trials as a treatment modality for metastatic prostate cancer therapy. 13,14,42 Both immunotherapy and targeted radiotherapy with J591 are being evaluated, and have thus far shown limited toxicity and no adverse immunologic effects. 13,14 These trials were undertaken when endothelial PSMA expression was thought to be limited to neoplastic neovasculature.…”

“…13,14,42 Both immunotherapy and targeted radiotherapy with J591 are being evaluated, and have thus far shown limited toxicity and no adverse immunologic effects. 13,14 These trials were undertaken when endothelial PSMA expression was thought to be limited to neoplastic neovasculature. Our current finding of PSMA expression in nonneoplastic neovasculature, and its likely role in vasculogenesis and angiogenesis associated with reparative and regenerative conditions, is important to consider when determining the enrollment criteria for clinical trials using anti-PSMA therapies, such as regarding patients with cardiovascular disease, diabetes, and asthma.…”

“…13,14 Materials and methods Using a protocol approved by the Institutional Review Board at the University of Chicago Medical Center, archival formalin-fixed paraffin-embedded tissue was obtained from keloids (15 cases), granulation tissue from heart valves (10 cases) and pleura (12 cases), proliferative endometrium (10 cases), and secretory endometrium (10 cases mid-secretory and 10 cases late secretory), as well as Barrett's mucosa with low-or high-grade dysplasia (12 foci and 24 foci, respectively) or no dysplasia (18 foci). Dysplastic foci in Barrett's mucosa were determined by three pathologists (IOG, AEN, and JH) who agreed on the diagnosis.…”