Development of meta-tetrahydroxyphenylchlorin-monoclonal antibody conjugates for photoimmunotherapy.

Abstract

A limitation of photodynamic therapy is the lack of tumor selectivity of the photosensitizer. To overcome this problem, a protocol was developed for coupling of meta-tetrahydroxyphenylchlorin (mTHPC), one of the most promising photosensitizers, to tumor-selective monoclonal antibodies (MAbs). mTHPC was radiolabeled with 131I to facilitate the assessment of the in vitro and in vivo behavior. After the modification to 131I-mTHPC-(CH2COOH)4, thus increasing the water solubility and creating a functional moiety suitable for coupling, conjugation was performed using a labile ester. Insoluble aggregates were not formed when mTHPC-MAb conjugates with a molar ratio of up to 4 were prepared. These conjugates showed a minimal impairment of the integrity on SDS-PAGE, full stability in serum in vitro, and an optimal immunoreactivity. To test the in vivo behavior of the mTHPC-MAb conjugates, the head and neck squamous cell carcinoma-selective chimeric MAb U36 was used in head and neck squamous cell carcinoma-bearing nude mice. Biodistribution data showed that the tumor selectivity of cMAb U36-conjugated mTHPC was increased in comparison with free mTHPC, despite the fact that conjugates with a higher mTHPC:MAb ratio were more rapidly cleared from the blood. Preliminary results on the in vitro efficacy of photodynamic therapy with MAb-conjugated mTHPC showed that mTHPC coupled to the internalizing murine MAb 425 exhibited more phototoxicity than when coupled to the noninternalizing chimeric MAb U36.

• Authors: M B Vrouenraets, G W Visser, F A Stewart, M Stigter, H Oppelaar, P E Postmus, G B Snow, G A van Dongen
• Journal: Cancer research (Cancer Res) Vol. 59 Issue 7 Pg. 1505-13 (Apr 01 1999) ISSN: 0008-5472 [Print] United States
• PMID: 10197621 (Publication Type: Journal Article)

Chemical References

• Antibodies, Monoclonal
• Immunoconjugates
• Iodine Radioisotopes
• Mesoporphyrins
• Photosensitizing Agents
• temoporfin

Topics

• Animals
• Antibodies, Monoclonal (pharmacokinetics, therapeutic use)
• Humans
• Immunoconjugates (therapeutic use)
• Iodine Radioisotopes
• Mesoporphyrins (pharmacokinetics, therapeutic use)
• Mice
• Photochemotherapy
• Photosensitizing Agents (therapeutic use)
• Tissue Distribution
• Tumor Cells, Cultured