Development of meta-tetrahydroxyphenylchlorin-monoclonal antibody conjugates for photoimmunotherapy

Maarten B. Vrouenraets, Gerard W M Visser, Fiona A. Stewart, Marijke Stigter, Hugo Oppelaar, Pieter E. Postmus, Gordon B. Snow, Guus A M S Van Dongen

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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.

Original languageEnglish
Pages (from-to)1505-1513
Number of pages9
JournalCancer Research
Issue number7
Publication statusPublished - 1 Apr 1999

Cite this

Vrouenraets, M. B., Visser, G. W. M., Stewart, F. A., Stigter, M., Oppelaar, H., Postmus, P. E., ... Van Dongen, G. A. M. S. (1999). Development of meta-tetrahydroxyphenylchlorin-monoclonal antibody conjugates for photoimmunotherapy. Cancer Research, 59(7), 1505-1513.