For the treatment of tumours and other proliferative conditions, widespread uptake of photodynamic therapy (PDT) has to some extent been hindered by its inability to target specifically photosensitisers (PSs) to localised lesions in the body. PSs may be deposited in the skin, leading to painful and disfiguring photosensitivity, sometimes for weeks after initial treatment. Targeting PSs specifically could not only avoid such side-effects, it could greatly improve PDT's therapeutic margin.
This review describes photoimmunoconjugates (PICs) produced via successful combination of PSs with recombinant monoclonal antibody fragments (sc-Fvs). PICs can not only target specifically and destroy tumour cells in vitro and in vivo, but counter-intuitively, it is possible to conjugate many more PSs to an sc-Fv than to the much larger parent monoclonal antibody.
The general utility of PICs is demonstrated by significant improvements to the potency and selectivity of already existing PSs. Furthermore, critical features of sc-Fvs are discussed that enable them to make effective PICs. This has implications for the future engineering of scFv carriers for PDT, in order to control the number and function of the PSs that can be coupled.
PervaizS. (2001) Reactive oxygen-dependent production of novel photochemotherapeutic agents. FASEB J., 15, 612–617.
10.
CoxJ. P. L., JankowskiK. J., KatzkyR., ParkerD., BeeleyN. R. A., HarrisonA., and WalkerC. (1989) Chem Commun., 797.
11.
JiangF. N., JiangS., LiuD. J., RichterA., and LevyJ. G. (1990) J. Immun. Meth., 134, 139.
12.
JiangF. N., LiuD., NeyndorffH., ChesterM., JiangS., and LevyJ. G. (1991) J. Natl. Cancer Inst., 83, 1218.
13.
EgorovYu. S., KrasnovskiiA. A.Jr., PapkovskiiD. B., PonomarevG. V., and SavitskiiA. P. (1990) Bull. Exp. Biol. Med., 109, 454.
14.
MilgromL. R., and O'NeillF. (1995) Towards synthetic-porphyin/monoclonal antibody conjugates. Tetrahedron, 51, 2137–2144.
15.
BrandF. X., RavanelN., GauchezA. S., PasquierD., PayanR., FagretD., and MousseauM. (2006) Prospect for anti-HER2 receptor therapy in breast cancer. Anticancer Res., 26, 463–470.
16.
van DongenG. A., VisserG. W., and VrouenraetsM. B. (2004) Photosensitizer-antibody conjugates for detection and therapy of cancer, Adv. Drug Deliv. Rev., 56, 31–52.
17.
MolpusK. L., HamblinM. R., RizviI., and HasanT. (2000) Intraperitoneal photoimmunotherapy of ovarian carcinoma xenografts in nude mice using charged photoimmunoconjugates. Gynecol. Oncol., 76, 397–404.
18.
VrouenraetsM. B., VisserG. W., StewartF. A., StigterM., OppelaarH., PostmusP. E., SnowG. B., and van DongenG. A. (1999) Development of meta-tetrahydroxyphenylchlorin-monoclonal antibody conjugates for photoimmunotherapy. Cancer Res., 59, 1505–1513.
19.
DoughertyT. J. (1993) Photodynamic therapy. Photochem. Photobiol., 58, 895–900.
20.
EmbletonM. L., NairS. P., CooksonB. D., and WilsonM. (2004) Antibody-directed photodynamic therapy of methicillin resistant Staphylococcus aureus. Microb. Drug Resist., 10, 92–97.
21.
SavellanoM. D., and HasanT. (2003) Targeting cells that over-express the epidermal growth factor receptor with polyethylene glycolated BPD verteporfm photosensitiser immunoconjugates. Photochem. Photobiol., 77, 431–439.
22.
HudsonR., CarcenacM., SmithK., MaddenL., ClarkeO. J., PelegrinA., GreenmanJ., and BoyleR.W. (2005) The development and characterisation of porphyrin isothiocyanate- monoclonal antibody conjugates for photoimmunotherapy. Br. J. Cancer, 92, 1442–1449.
23.
VrouenraetsM. B., VisserG. W., LoupC., MeunierB., StigterM., OppelaarH., StewartF. A., SnowG. B., and van DongenG. A. (2000) Targeting of a hydrophilic photosensitiser by use of internalizing monoclonal antibodies, A new possibility for use in photodynamic therapy. Int. J. Cancer, 88, 108–114.
24.
AvelineB. M., HasanT., and RedmondR. W. (1995) The effects of aggregation, protein binding and cellular incorporation on the photophysical properties of benzoporphyrin derivative monoacid ring A (BPDMA). J. Photochem. Photobiol., B, 30, 161–169.
25.
KuimovaM. K., BhattiM., DeonarainM. P., YahiogluG., LevittJ. A., StamatiI., SuhlingK., and PhillipsD. (2007) Fluorescence characterisation of multiply-loaded anti-HER2 single-chain Fv-photosensitiser conjugates suitable for photodynamic therapy. Photochem. Photobiol. Sci., 6, 933–939.
26.
BhattiM., YahiogluG., MilgromI. R., Garcia-MayaM., ChesterK. A., and DeonarainM. P. (2008) Targeted photodynamic therapy with multiply loaded recombinant antibody fragments. Int. J. Cancer, 122, 1155–1163.
27.
AdamsG. P., SchierR., MarshallK., WolfE. J., McCallA. M., MarksJ. D., and WeinerL. M. (1999) Increased affinity leads to improved selective tumour delivery of single-chain Fv antibodies. Cancer Res., 58, 485–490.
28.
HendriksB. S., OpreskoL. K., WileyH. S., and LauffenburgerD. (2003) Quantitative analysis of HER2-mediated effects on HER2 and epidermal growth factor receptor endocytosis, distribution of homo-and heterodimers depends on relative HER2 levels. J. Biol. Chem., 278, 23343–23351.
29.
SavellanoM. D., PogueB. W., HoopesP. J., VitettaE. S., and PaulsenK. D. (2005) Multiepitope HER2 targeting enhances photoimmunotherapy of HER2-overexpressing cancer cells with pyropheophorbide-a immunoconjugates. Cancer Res., 65, 6371–6379.
30.
KhuranaM., CollinsH. A., KarotkiA., AndersonH. L., CrambD. T., and WilsonB. C. (2007) Quantitative in vitro demonstration of two-photon photodynamic therapy using Photofrin® and Visudyne®. Photochem. Photobiol., 83, 1441–1448.
31.
BatraS. K., JainM., WittelU. A., ChauhanS. C., and ColcherD. (2002) Pharmacokinetics and biodistribution of genetically engineered antibodies. Curr Opin. Biotechnol., 13, 603–608.
32.
ChesterK. A., BhatiaJ., BoxerG., CookeS. P., FlynnA. A., HuhalovA., MayerA., PedleyR. B., RobsonL., SharmaS. K., SpencerD. I., and BegentR. H. (2000) Clinical applications of phage-derived sc-Fvs and sc-Fv fusion proteins. Dis. Markers, 16, 53–62.
33.
BirchlerM., VitiF., ZardiL., SpiessB., and NeriD. (1999) Selective targeting and photocoagulation of ocular angiogenesis mediated by a phage-derived human antibody fragment. Nat. Biotechnol., 17, 984–988.
34.
FabbriniM., TrachselE., SoldaniP., BindiS., AlessiP., BracciL., KosmehlH., ZardiL., NeriD., and NeriP. (2006) Selective occlusion of tumour blood vessels by targeted delivery of an anti-bodyphotosensitiser conjugate. Int. J. Cancer, 118, 1805–1823.
35.
BegentR. H., VerhaarM. I., ChesterK. A., CaseyJ. L., GreenA. J., NapierM. P., Hope-StoneL. D., CushenN., KeepP. A., JohnsonC. J., HawkinsR. E., HilsonA. J., and RobsonL. (1996) Clinical evidence of efficient tumour targeting based on single-chain Fv antibody selected from a combinatorial library. Nat. Med., 2, 979–984.
36.
AdamsG. P., SchierR., MarshallK., WolfE. I., McCallA. M., MarksJ. D., and WeinerL. M. (1999) Increased affinity leads to improved selective tumour delivery of single-chain Fv antibodies. Cancer Res., 58, 485–490.
37.
HaddadR., KaplanO., GreenbergR., SiegalA., SkornickY., and KashtanH. (2000) Photodynamic therapy of murine colon cancer and melanoma using systemic aminolevulinic acid as a photosensitiser. Int. J. Surg. Investig., 2, 171–178.
38.
CuencaR. E., AllisonR. R., SibataC., and DownieG. H. (2004) Breast cancer with chest wall progression, treatment with photodynamic therapy. Ann. Surg. Oncol., 11, 322–327.
39.
MuschterR. (2003) Photodynamic therapy, a new approach to prostate cancer. Curr Urol. Rep., 4, 221–228.
40.
HackbarthS., HornefferV., WieheA., HillenkampF., and RoderB. (2001) Photophysical properties of pheophorbide-a substituted with a diamonobuta-nepolypropylene-imine dendrimer. Chem. Phys., 269, 339–346.
41.
RenardM., BelkadiL., and BedouelleH. (2003) Deriving topological constraints from functional data for the design of reagent-less fluorescent immunosensors. J. Mol. Biol., 326, 167–175.
42.
PeerD., KarpJ. M., HongS., FarokhzadO. C., MargalitR., and LangerR. (2007) Nature Nanotechnol., 2, 751–760.
