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Comparison of aluminium (III) phthalocyanine tetrasulfonate‐ and meta‐tetrahydroxyphenylchlorin‐monoclonal antibody conjugates for their efficacy in photodynamic therapy in vitro
Author(s) -
Vrouenraets Maarten B.,
Visser Gerard W.M.,
Stigter Marÿke,
Oppelaar Hugo,
Snow Gordon B.,
van Dongen Guus A.M.S.
Publication year - 2002
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.10281
Subject(s) - phototoxicity , photosensitizer , photodynamic therapy , conjugate , monoclonal antibody , chemistry , internalization , in vitro , cell culture , in vivo , cytotoxicity , cancer research , cell , antibody , biophysics , microbiology and biotechnology , biochemistry , biology , immunology , photochemistry , organic chemistry , mathematical analysis , genetics , mathematics
A challenge in photodynamic therapy (PDT) is to improve the tumour selectivity of the photosensitizers by using monoclonal antibodies (MAbs). With this aim, we developed MAb‐conjugates with the hydrophobic photosensitizer meta ‐tetrahydroxyphenylchlorin ( m THPC) and with the hydrophilic sensitizer aluminium (III) phthalocyanine tetrasulfonate (AlPcS 4 ). The capacity of these photoimmunoconjugates for selective targeting of squamous cell carcinoma (SCC) in vivo was demonstrated previously in SCC‐bearing nude mice. Preliminary in vitro PDT studies with the vulvar SCC cell line A431 showed promising phototoxicity with both sensitizers when coupled to the internalizing MAb 425. To rank the photosensitizers for their potential in photoimmunotherapy, we herein describe an extensive in vitro evaluation of m THPC‐MAb and AlPcS 4 ‐MAb conjugates. Both classes of conjugates were directly compared using 5 different SCC cell lines as target and 3 different MAbs (BIWA 4, E48 and 425) for tumour cell targeting. In contrast to free AlPcS 4 (IC 50 ≥ 700 nM), MAb‐conjugated AlPcS 4 was found to be highly phototoxic in PDT in all 5 cell lines. AlPcS 4 ‐BIWA 4 was most consistently effective with IC 50 values ranging from 0.06–5.4 nM. m THPC‐MAb conjugates were in general hardly effective. Phototoxicity (log IC 50 ) of the AlPcS 4 ‐MAb conjugates was found to be strongly correlated with their total cell binding capacity (internalized and surface bound) and to be less correlated with their internalization capacity. In conclusion, these data show a high potential of AlPcS 4 ‐MAb conjugates in comparison to m THPC‐MAb conjugates for use in PDT. © 2002 Wiley‐Liss, Inc.