Targeting, imaging, and therapy using a humanized antiprostate stem cell antigen (PSCA) antibody

Area of Science:

• Oncology
• Immunology
• Biotechnology

Background:

• The murine 1G8 monoclonal antibody targets prostate stem cell antigen (PSCA), inhibiting prostate tumor growth in preclinical models.
• Further development is needed to enhance targeting properties and clinical applicability for urogenital cancers.

Purpose of the Study:

• To develop and evaluate a humanized version of the 1G8 antibody (hu1G8) for improved targeting and therapeutic efficacy against PSCA-expressing tumors.
• To assess the in vivo performance of hu1G8 for imaging and therapy in preclinical models of prostate and bladder cancer.

Main Methods:

• Radiolabeling of murine 1G8 with In-111 for initial targeting evaluation.
• Production of a chimeric 1G8 antibody and subsequent humanization to create hu1G8 variants.
• Affinity assessment using Biacore and in vivo tumor targeting evaluation via microPET imaging with I-labeled hu1G8-B.
• Assessment of antitumor efficacy of hu1G8-B in xenograft models of prostate and bladder cancer.

Main Results:

• Radiolabeled micro1G8 showed specific uptake in PC3-PSCA xenografts.
• Humanized hu1G8-B demonstrated specific tumor targeting in PC3-PSCA and LAPC-9 xenografts with significant uptake.
• hu1G8-B significantly inhibited tumor growth in SW-780-PSCA bladder carcinoma xenografts where micro1G8 was ineffective.

Conclusions:

• The humanized 1G8 antibody (hu1G8-B) exhibits specific tumor targeting and potent antitumor activity against PSCA-expressing tumors.
• hu1G8-B demonstrates superior efficacy compared to the murine version, particularly in models with low PSCA expression.
• These findings support the further development of hu1G8 for targeted imaging and therapy of urogenital malignancies.