Photosensitizer-antibody conjugates for detection and therapy of cancer

doi:10.1016/j.addr.2003.09.003

Advanced Drug Delivery Reviews

Volume 56, Issue 1, 13 January 2004, Pages 31-52

https://doi.org/10.1016/j.addr.2003.09.003 Get rights and content

Abstract

Photodynamic therapy (PDT) is a promising approach for the treatment of superficially localized tumors. A limitation, however, is the lack of selectivity of the photosensitizers, which can result in severe toxicity. In this overview, the possibilities for using monoclonal antibodies (MAbs) for selective delivery of photosensitizers to tumors, are discussed. This approach is called photoimmunotherapy (PIT). For PIT to be successful, sufficient amounts of sensitizer should be coupled to the MAb without altering its biological properties. A challenging aspect herein is the hydrophobicity of therapeutic photosensitizers. Options for direct and indirect coupling of photosensitizers to MAbs are evaluated, while pros and cons are indicated. Special attention is paid to the quality testing of photoimmunoconjugates, as this information is important for further optimization of PIT. Results obtained thus far with PIT in in vitro and in vivo model systems are discussed. Despite the encouraging progress made, showing the high selectivity of photoimmunoconjugates, PIT still awaits initial clinical evaluation.

Introduction

Photodynamic therapy (PDT) is a therapeutic modality especially applied for the treatment of superficially localized tumors. In this approach, a photosensitive dye (photosensitizer) is injected intravenously (i.v.) or intraperitoneally (i.p.), where after it accumulates more or less selectively in the tumor. Due to the higher sensitizer concentration in the tumor compared to surrounding normal tissue, the tumor can be visualized by sensitizer fluorescence. For therapeutic application, the tumor becomes exposed to laser light, whereby the excitation of the photosensitizer results in the production of reactive species such as singlet oxygen, which are toxic for the tumor [1]. Light in the red or near-infrared region is used with a wavelength, which is maximally absorbed by the sensitizer. This maximum absorption wavelength of the sensitizer is an important parameter in PDT, since light of a longer wavelength penetrates deeper in the tissue, thereby making treatment of larger tumors possible. Another approach facilitating the treatment of larger tumors is the use of interstitial illumination techniques. PDT has been applied clinically for the treatment of a variety of tumor types [2]. The most promising results thus far have been obtained in head and neck and esophagus cancer, locoregional breast cancer recurrences and basal cell carcinoma. PDT has also attracted attention in relation to several other clinical applications, but these will not be subjects of the present overview.

Despite its promising results, current PDT leaves much to be desired. A limitation is the lack of selectivity of the photosensitizers, which can result in severe normal tissue damage after PDT of large surface areas, like in the treatment of disseminated i.p. tumors or mesothelioma. Furthermore, PDT can result in skin phototoxicity, with the consequence that patients must stay out of bright sunlight for several weeks following the administration of the photosensitizer. An option to overcome these problems is to couple the photosensitizer to monoclonal antibodies (MAbs) directed to tumor-associated antigens. This so-called photoimmunotherapy (PIT) aims at the selective delivery of photosensitizers to the tumor. With this approach the problem of cutaneous phototoxicity might be reduced, as the skin is poorly permeable for macromolecules like immunoglobulins (vide infra).

Section snippets

Critical targets for photodynamic effects

The potentially critical cellular and subcellular targets for PDT have been intensively studied with unconjugated photosensitizers. Besides direct cell killing as a result of phototoxic cell damage, indirect effects also seem to play an important role in the destruction of tumor tissue. This information might be important, when aiming to hit the hypersensitive cellular and subcellular sites with PIT. Since singlet oxygen has a short lifetime (<0.04 μs) and a radius of action (<0.02 μm), which

Tumor targeting with monoclonal antibodies (MAbs)

Several factors are known to affect the efficiency of tumor targeting by MAbs in vivo. These factors are related to the antigenic target, the MAb, as well as the tumor. Before results on the production of photosensitizer-MAb conjugates and the evaluation of these conjugates in in vitro and in vivo models are summarized, the influence of each of these factors on the efficiency of targeting will be discussed.

Photosensitizers for targeting

A large number of photosensitizers have been evaluated in PDT experiments. In this section, we limit ourselves by summarizing the characteristics of the sensitizers, which have frequently been used in PDT as well as in PIT, and still are attracting attention nowadays.

Development of photoimmunoconjugates

MAbs have been recognized as attractive carrier molecules for selective delivery of photosensitizers to tumors. However, several obstacles have to be faced in the development of high quality photoimmunoconjugates, i.e. conjugates in which the MAb is loaded with photosensitizer without loss or alteration of its biological properties. The photosensitizer of choice should contain a functional moiety for direct or indirect covalent linking to the lysine [54], [55], [56], [57], [58], [59], [60], [61]

Testing the quality of photoimmunoconjugates

The success of PIT will, among others, depend on the quality of the photoimmunoconjugates with respect to tumor selectivity and degree of accumulation. Before reviewing the results obtained with PIT thus far, we first will discuss some of the quality tests exploited to evaluate (i) the reproducibility of the conjugate production, (ii) the integrity and antigen binding capacity of the MAb upon coupling of the photosensitizer, (iii) the tumor targeting capacity of the conjugate, (iv) the efficacy

Photoimmunoconjugates for tumor detection

The use of MAbs for selective delivery of photosensitizer to tumors has been studied for about 20 years. The most convincing proof that MAbs are well qualified for this purpose, has been obtained in studies on photoimmunodetection. In 1991, Pèlegrin et al. [56] described the direct coupling of fluorescein to an anti-CEA MAb, and the evaluation of the conjugates in mice bearing established human colon carcinoma xenografts. Fluorescein was covalently coupled to the ¹²⁵I-labeled MAb at

Photoimmunotherapy with HpD-MAb conjugates

The first in vitro and in vivo studies, showing that photoimmunoconjugates had superior selective anti-tumor effects in PIT over drug or MAb alone, were described about 20 years ago [109], [110]. For this purpose, the group of Levy in Vancouver, Canada, coupled HpD directly to an anti-myosarcoma MAb by carbodiimide catalyzed peptide bond formation. Their reported substitution ratio of about 60, is much higher than would have been expected based on the number of amino groups present in a MAb

Conclusions

During the last decade conjugated and unconjugated MAbs became part of the armature used for diagnosis and treatment of cancer. MAbs are also capable for selective delivery of photosensitizers to tumors, as was best illustrated in photoimmunodetection studies. In the initial studies with fluorescein, conjugates with a high photosensitizer:MAb ratio were used to obtain high amounts of dye molecules in the tumor, sufficient for visualization. However, the in vivo tumor targeting potential of

References (110)

S.M. Chiu et al.
Phthalocyanine 4 photodynamic therapy-induced apoptosis of mouse L5178Y-R cells results from a delayed but extensive release of cytochrome c from mitochondria
Cancer Lett.
(2001)
V.O. Melnikova et al.
Subcellular localization of meta-tetra(hydroxyphenyl)chlorin in human tumor cells subjected to photodynamic treatment
J. Photochem. Photobiol. B
(1999)
C.M.N. Yow et al.
Cellular uptake, subcellular localization and photodamaging effect of Temoporfin (mTHPC) in nasopharyngeal carcinoma cells: comparison with hematoporphyrin derivative
Cancer Lett.
(2000)
A.S. Sobolev et al.
Targeted intracellular delivery of photosensitizers
Prog. Biophys. Mol. Biol.
(2000)
T. Kretzschmar et al.
Antibody discovery: phage display
Curr. Opin. Biotechnol.
(2002)
D.J. Hicklin et al.
Monoclonal antibody strategies to block angiogenesis
Drug Discov. Today
(2001)
P.J. Hudson
Recombinant antibody constructs in cancer therapy
Curr. Opin. Oncol.
(1999)
S.K. Batra et al.
Pharmacokinetics and biodistribution of genetically engineered antibodies
Curr. Opin. Biotechnol.
(2002)
S.-A. Kellermann et al.
Antibody discovery: the use of transgenic mice to generate monoclonal antibodies for therapeutics
Curr. Opin. Biotechnol.
(2002)
M. Trikha et al.
Monoclonal antibodies as therapeutics in oncology
Curr. Opin. Biotechnol.
(2002)

G.A. Kostenich et al.

Experimental grounds for using chlorin e₆ in the photodynamic therapy of malignant tumors

J. Photochem. Photobiol. B

(1994)

M. Ambroz et al.

Preparative, analytical and fluorescence spectroscopic studies of sulphonated aluminum phthalocyanine photosensitizers

J. Photochem. Photobiol. B

(1991)

F.N. Jiang et al.

Development of technology for linking photosensitizers to a model monoclonal antibody

J. Immunol. Methods

(1990)

K.L. Molpus et al.

Intraperitoneal photoimmunotherapy of ovarian carcinoma xenografts in nude mice using charged photoimmunoconjugates

Gynecol. Oncol.

(2000)

T. Hasan et al.

Monoclonal antibody-chromophore conjugates as selective phototoxins

J. Control. Release

(1989)

S.F. Wolfort et al.

Control of hypertrophic scar growth using antibody-targeted photolysis

J. Surg. Res.

(1996)

M.A. Slinkin et al.

Biodistribution of anti-CEA F(ab′)2 fragments conjugated with chelating polymers: influence of conjugate electron charge on tumor uptake and blood clearance

Nucl. Med. Biol.

(1993)

W.M. Pardridge et al.

Cationization of a monoclonal antibody to the human immunodeficiency virus REV protein enhances cellular uptake but does not impair antigen binding of the antibody

Immunol. Lett.

(1994)

K.R. Weishaupt et al.

Identification of singlet oxygen as the cytotoxic agent in photoinactivation of a murine tumor

Cancer Res.

(1976)

M.B. Vrouenraets et al.

Basic principles, applications in oncology and improved selectivity of photodynamic therapy

Anticancer Res.

(2003)

J. Moan et al.

The photodegradation of porphyrins in cells can be used to estimate the lifetime of singlet oxygen

Photochem. Photobiol.

(1991)

R. Nilsson et al.

Primary mechanisms of erythrocyte photolysis induced by biological sensitizers and phototoxic drugs

Photochem. Photobiol.

(1975)

B.C. Wilson et al.

Subcellular localization of Photofrin® and aminolevulinic acid and photodynamic cross-resistance in vitro in radiation-induced fibrosarcoma cells sensitive or resistant to Photofrin-mediated photodynamic therapy

Photochem. Photobiol.

(1997)

K.W. Woodburn et al.

Subcellular localization of porphyrins using confocal laser scanning microscopy

Photochem. Photobiol.

(1991)

K.W. Woodburn et al.

Evaluation of porphyrin characteristics required for photodynamic therapy

Photochem. Photobiol.

(1992)

C. Fabris et al.

Photosensitization with zinc(II) phthalocyanine as a switch in the decision between apoptosis and necrosis

Cancer Res.

(2001)

L. Ma et al.

Evaluation of a new photosensitizer, meso-tetra-hydroxyphenyl-chlorin, for use in photodynamic therapy: a comparison of its photobiological properties with those of two other photosensitizers

Int. J. Cancer

(1994)

J.Y. Chen et al.

A comparison of the photodynamic effects of temoporfin (mTHPC) and MC540 on leukemia cells: efficacy and apoptosis

Photochem. Photobiol.

(1998)

N. Ramakrishnan et al.

DNA lesions and DNA degradation in mouse lymphoma L5178Y cells after photodynamic treatment sensitized by chloroaluminium phthalocyanine

Photochem. Photobiol.

(1989)

T.J. Dougherty et al.

Photodynamic therapy

J. Natl. Cancer Inst.

(1998)

K.S. McMahon et al.

Effects of photodynamic therapy using mono-l-aspartyl chlorin e₆ on vessel constriction, vessel leakage, and tumor response

Cancer Res.

(1994)

V.H. Fingar et al.

The effects of thrombocytopenia on vessel stasis and macromolecular leakage after photodynamic therapy using

Photofrin Photochem. Photobiol.

(1997)

V.H. Fingar et al.

The effects of photodynamic therapy using differently substituted zinc phthalocyanines on vessel constriction, vessel leakage, and tumor response

Photochem. Photobiol.

(1993)

G. Krosl et al.

Induction of immune cell infiltration into murine SCCVII tumour by Photofrin-based photodynamic therapy

Br. J. Cancer

(1995)

G. Köhler et al.

Continuous cultures of fused cells secreting antibody of predefined specificity

Nature

(1975)

S. Welt et al.

Antibody targeting in metastatic colon cancer: a phase I study of monoclonal antibody F19 against a cell-surface protein of reactive tumor stromal fibroblasts

J. Clin. Oncol.

(1994)

J.A. Posey et al.

A pilot trial of Vitaxin, a humanized anti-vitronectin receptor (anti-αvβ3) antibody in patients with metastatic cancer

Cancer Biother. Radiopharm.

(2001)

M. Santimaria et al.

Immunoscintigraphic detection of the AD-B domain of fibronectin, a marker of angiogenesis, in patients with cancer

Clin. Cancer Res.

(2003)

R. de Bree et al.

Biodistribution of radiolabeled monoclonal antibody E48 IgG and F(ab′)₂ in patients with head and neck cancer

Clin. Cancer Res.

(1995)

L.M. Cobb

Intratumour factors influencing the access of antibody to tumour cells

Cancer Immunol. Immunother.

(1989)

R.K. Jain

Vascular and interstitial barriers to delivery of therapeutic agents in tumors

Cancer Metastasis Rev.

(1990)

R.K. Jain

Transport of molecules in the tumor interstitium: a review

Cancer Res.

(1997)

J.F. Chatal et al.

Biodistribution of indium-111-labeled OC125 monoclonal antibody intraperitoneally injected into patients operated on for ovarian cancers

Cancer Res.

(1989)

R. de Bree et al.

The impact of tumour volume and other characteristics on uptake of radiolabelled monoclonal antibodies in tumour tissue of head and neck cancer patients

Eur. J. Nucl. Med.

(1998)

W.C. Buijs et al.

Dosimetric analysis of chimeric monoclonal antibody cMOv18 IgG in ovarian carcinoma patients after intraperitoneal and intravenous administration

Eur. J. Nucl. Med.

(1998)

P. Carter

Improving the efficacy of antibody-based cancer therapies

Nat. Rev. Cancer

(2001)

T. Gura

Magic bullets hit the target

Nature

(2002)

R.L. Lipson et al.

The use of a derivative of haematoporphyrin in tumor detection

J. Natl. Cancer Inst.

(1961)

T.J. Dougherty et al.

Photoradiation therapy: II. Cure of animal tumours with hematoporphyrin and light

J. Natl. Cancer Inst.

(1975)

J.F. Kelly et al.

Photodynamic destruction of human bladder carcinoma

Br. J. Cancer

(1975)

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Photosensitizer-antibody conjugates for detection and therapy of cancer

Abstract

Introduction

Section snippets

Critical targets for photodynamic effects

Tumor targeting with monoclonal antibodies (MAbs)

Photosensitizers for targeting

Development of photoimmunoconjugates

Testing the quality of photoimmunoconjugates

Photoimmunoconjugates for tumor detection

Photoimmunotherapy with HpD-MAb conjugates

Conclusions

Cancer Lett.

J. Photochem. Photobiol. B

Cancer Lett.

Prog. Biophys. Mol. Biol.

Curr. Opin. Biotechnol.

Drug Discov. Today

Curr. Opin. Oncol.

Curr. Opin. Biotechnol.

Curr. Opin. Biotechnol.

Curr. Opin. Biotechnol.

J. Photochem. Photobiol. B

J. Photochem. Photobiol. B

J. Immunol. Methods

Gynecol. Oncol.

J. Control. Release

J. Surg. Res.

Nucl. Med. Biol.

Immunol. Lett.

Identification of singlet oxygen as the cytotoxic agent in photoinactivation of a murine tumor

Cancer Res.

Basic principles, applications in oncology and improved selectivity of photodynamic therapy

Anticancer Res.

The photodegradation of porphyrins in cells can be used to estimate the lifetime of singlet oxygen

Photochem. Photobiol.

Primary mechanisms of erythrocyte photolysis induced by biological sensitizers and phototoxic drugs

Photochem. Photobiol.

Subcellular localization of Photofrin® and aminolevulinic acid and photodynamic cross-resistance in vitro in radiation-induced fibrosarcoma cells sensitive or resistant to Photofrin-mediated photodynamic therapy

Photochem. Photobiol.

Subcellular localization of porphyrins using confocal laser scanning microscopy

Photochem. Photobiol.

Evaluation of porphyrin characteristics required for photodynamic therapy

Photochem. Photobiol.

Photosensitization with zinc(II) phthalocyanine as a switch in the decision between apoptosis and necrosis

Cancer Res.

Evaluation of a new photosensitizer, meso-tetra-hydroxyphenyl-chlorin, for use in photodynamic therapy: a comparison of its photobiological properties with those of two other photosensitizers

Int. J. Cancer

A comparison of the photodynamic effects of temoporfin (mTHPC) and MC540 on leukemia cells: efficacy and apoptosis

Photochem. Photobiol.

DNA lesions and DNA degradation in mouse lymphoma L5178Y cells after photodynamic treatment sensitized by chloroaluminium phthalocyanine

Photochem. Photobiol.

Photodynamic therapy

J. Natl. Cancer Inst.

Effects of photodynamic therapy using mono-l-aspartyl chlorin e6 on vessel constriction, vessel leakage, and tumor response

Cancer Res.

The effects of thrombocytopenia on vessel stasis and macromolecular leakage after photodynamic therapy using

Photofrin Photochem. Photobiol.

The effects of photodynamic therapy using differently substituted zinc phthalocyanines on vessel constriction, vessel leakage, and tumor response

Photochem. Photobiol.

Induction of immune cell infiltration into murine SCCVII tumour by Photofrin-based photodynamic therapy

Br. J. Cancer

Continuous cultures of fused cells secreting antibody of predefined specificity

Nature

Antibody targeting in metastatic colon cancer: a phase I study of monoclonal antibody F19 against a cell-surface protein of reactive tumor stromal fibroblasts

J. Clin. Oncol.

A pilot trial of Vitaxin, a humanized anti-vitronectin receptor (anti-αvβ3) antibody in patients with metastatic cancer

Cancer Biother. Radiopharm.

Immunoscintigraphic detection of the AD-B domain of fibronectin, a marker of angiogenesis, in patients with cancer

Clin. Cancer Res.

Biodistribution of radiolabeled monoclonal antibody E48 IgG and F(ab′)2 in patients with head and neck cancer

Clin. Cancer Res.

Intratumour factors influencing the access of antibody to tumour cells

Cancer Immunol. Immunother.

Vascular and interstitial barriers to delivery of therapeutic agents in tumors

Cancer Metastasis Rev.

Transport of molecules in the tumor interstitium: a review

Cancer Res.

Biodistribution of indium-111-labeled OC125 monoclonal antibody intraperitoneally injected into patients operated on for ovarian cancers

Cancer Res.

Effects of photodynamic therapy using mono-l-aspartyl chlorin e₆ on vessel constriction, vessel leakage, and tumor response

Biodistribution of radiolabeled monoclonal antibody E48 IgG and F(ab′)₂ in patients with head and neck cancer