Towards recombinant antibody-fragment targeted photodynamic therapy.
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.
Department of Life Sciences, Biochemistry Building, Imperial College London, UK. lionel.milgrom@hotmail.com
Lionel R
LR
Milgrom
D000595:Amino Acid Sequence; D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D006801:Humans; D018796:Immunoconjugates / Q000627:therapeutic use*; D007128:Immunoglobulin Fragments / Q000627:therapeutic use; D009369:Neoplasms / Q000188:drug therapy; D010778:Photochemotherapy; D017319:Photosensitizing Agents / Q000627:therapeutic use*; D011994:Recombinant Proteins / Q000627:therapeutic use
D000911:Antibodies, Monoclonal; D018796:Immunoconjugates; D007128:Immunoglobulin Fragments; D017319:Photosensitizing Agents; D011994:Recombinant Proteins