Rapid diagnostic imaging and targeted immunotoxin delivery in aggressive prostate cancer using CEACAM5-specific...

Area of Science:

• Oncology
• Molecular Biology
• Immunotherapy

Background:

• Aggressive variant prostate cancer (AVPC) arises from metastatic prostate cancer (mPCa) after treatment, presenting diverse subtypes like castration-resistant prostate cancer (CRPC).
• Carcinoembryonic antigen-related cell adhesion molecule 5 (CEACAM5) is highly expressed in AVPC, including neuroendocrine prostate carcinoma (NEPC) and double-negative prostate carcinoma (DNPC), indicating its potential as a therapeutic target.
• Effective treatments for AVPC are limited due to a scarcity of well-defined molecular targets.

Purpose of the Study:

• To identify and validate CEACAM5 as a target for imaging and therapy in aggressive variant prostate cancer.
• To develop a high-affinity nanobody (B12) targeting CEACAM5 for enhanced tumor visualization and drug delivery.
• To evaluate the therapeutic efficacy of a CEACAM5-targeting immunotoxin (B12-PE38) and its combination with standard chemotherapy.

Main Methods:

• Phage library screening was employed to discover a high-affinity nanobody (B12) specific to CEACAM5.
• In vivo studies utilized B12 for rapid imaging of AVPC and assessed the anti-tumor activity of B12-PE38 in AVPC xenograft models, including those mimicking bone metastasis.
• Combination therapy involving B12-PE38 and docetaxel was evaluated for enhanced tumor inhibition.

Main Results:

• The nanobody B12 demonstrated strong binding, enhanced tumor accumulation, and effective tissue penetration for in vivo AVPC imaging.
• The immunotoxin B12-PE38 exhibited significant anti-tumor activity in AVPC xenograft models.
• Combining B12-PE38 with docetaxel resulted in enhanced tumor inhibition and progression delay.

Conclusions:

• CEACAM5 is a viable and promising target for precise imaging and targeted therapy in aggressive variant prostate cancer.
• The CEACAM5-specific nanobody B12 offers a novel platform for diagnostic imaging and targeted drug delivery.
• The B12-PE38 immunotoxin, particularly in combination with docetaxel, presents a potential new therapeutic strategy for AVPC, addressing the current lack of effective treatments.