Photoimmunotherapy targeting prostate-specific membrane antigen: are antibody fragments as effective as antibodies?

Abstract

UNLABELLED:

Photoimmunotherapy is a highly cell-selective cancer therapy based on an armed antibody conjugate with a phthalocyanine-based photosensitizer, IR700. Photoimmunotherapy induces rapid and highly specific necrosis in targeted cancer cells after exposure to near-infrared (NIR) light. Cells not expressing the antigen are not affected. To date, photoimmunotherapy has been demonstrated only with full antibody-IR700 conjugates. In this study, small and bivalent antibody fragments, including anti-prostate-specific membrane antigen (PSMA) diabody (Db) and minibody (Mb), were compared with intact IgG for their effectiveness as photoimmunotherapy agents.

METHODS:

Radioiodinated antibody and antibody fragments with (125)I were used to determine the timing of maximum binding of each anti-PSMA antibody fragment on the cell surface in vivo in mice bearing either PSMA-positive or -negative PC3 tumors. Then therapeutic efficacy of photoimmunotherapy was examined by exposing mice to NIR light at 2 time points based on the time of maximum cell surface binding at 6 h after injection for Db-IR700 and 24 h after injection for Mb-IR700 and IgG-IR700 as well as 24 h after the peak uptake times.

RESULTS:

Photoimmunotherapy with the same molar concentration of PSMA-Db-IR700, PSMA-Mb-IR700, and PSMA-IgG-IR700 conjugate showed similar therapeutic effects in vitro and in vivo on PSMA-positive PC3 tumor xenografts in cytotoxicity and survival curves (P > 0.05).

CONCLUSION:

The use of PSMA-Db-IR700 conjugate results in the shortest time interval between injection and NIR exposure without compromising therapeutic effects of photoimmunotherapy.

• Authors: Rira Watanabe, Hirofumi Hanaoka, Kazuhide Sato, Tadanobu Nagaya, Toshiko Harada, Makoto Mitsunaga, Insook Kim, Chang H Paik, Anna M Wu, Peter L Choyke, Hisataka Kobayashi
• Journal: Journal of nuclear medicine : official publication, Society of Nuclear Medicine (J Nucl Med) Vol. 56 Issue 1 Pg. 140-4 (Jan 2015) ISSN: 1535-5667 [Electronic] United States
• PMID: 25500827 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, N.I.H., Intramural)
• Copyright: © 2015 by the Society of Nuclear Medicine and Molecular Imaging, Inc.

Chemical References

• Antigens, Surface
• Immunoconjugates
• Immunoglobulin Fragments
• Indoles
• Isoindoles
• Photosensitizing Agents
• FOLH1 protein, human
• Glutamate Carboxypeptidase II
• phthalocyanine

Topics

• Animals
• Antigens, Surface (immunology)
• Cell Line, Tumor
• Cell Proliferation (drug effects, radiation effects)
• Female
• Glutamate Carboxypeptidase II (immunology)
• Humans
• Immunoconjugates (therapeutic use)
• Immunoglobulin Fragments (chemistry, immunology, therapeutic use)
• Immunotherapy (methods)
• Indoles (chemistry, pharmacology)
• Infrared Rays
• Isoindoles
• Male
• Mice
• Necrosis (chemically induced)
• Photosensitizing Agents (chemistry, pharmacology)
• Prostatic Neoplasms (pathology, therapy)
• Tissue Distribution