A principle objective in
chemotherapy is the development of modalities capable of selectively destroying malignant cells while sparing normal tissues. One new approach to selective
photochemotherapy, antibody-targeted photolysis (ATPL) uses
photosensitizers (PS) coupled to
monoclonal antibodies (MAbs) which bind to
cell surface antigens on malignant cells. Selective destruction of human T
leukemia cells (HBP-ALL) was accomplished by coupling the efficient PS
chlorin e(6) to an
anti-T cell MAb using
dextran carriers. Conjugates with
chlorin: MAb ratios of 30:1 retained > 85% MA b binding activity, and had a quantum yield for
singlet oxygen production of 0.7 +/- 0.1, the same as that of free
chlorin e(6). Cell killing was dependent on the doses of both MAb-PS and 630-670 nm light and occurred only in target cell populations which bound the MAb. On the order of 10(10)
singlet oxygen molecules were necessary to kill a cell. A second approach to specific
photochemotherapy, selective
carcinoma cell photolysis (SCCP), relies on preferential accumulation of certain cationic PS by
carcinoma cell mitochondria. We have evaluated several classes of cationic
dyes, and in the case of N,N'-bis-(2-ethyl-1,3-dioxolane)-kryptocyanine (
EDKC) and some of its analogs, have demonstrated highly selective killing of human squamous cell, bladder and colon
carcinoma cells in vitro. In isolated mitochondria,
EDKC uptake and fluorescence depended on membrane potential, and the
dye specifically photosensitized damage to Complex I in the electron transport chain. N,N'-bis-(2-ethyl-1,3-dioxolane)-kryptocyanine and some of its analogs accumulated within subcutaneous xenografts of human
tumors in nude mice with
tumor:skin ratios > 8. Photoirradiation caused significant inhibition of
tumor growth, without cutaneous
phototoxicity.