Targetted phototherapy with sensitizer-monoclonal antibody conjugate and light.
Photodynamic therapy (PDT) was performed in vitro and in vivo using monoclonal antibody conjugated to hematoporphyrin (HP). The antibody (45-2D9) recognized a cell surface glycoprotein on cells derived from NIH 3T3 cells which were transformed with the ras oncogene (45-342). Radionuclide imaging with either In111 or I125 chelated to 45-2D9 or the isotype identical (IgG1) antibody MOPPC-21 revealed selectivity of 45-2D9 for 45-342 flank tumours in nude mice, and minimal targetting for a 45-342 clone which did not express the cell surface glycoprotein. The 45-2D9-HP conjugate resulted in selective killing of the 45-342 line compared with the parent line in vitro. At HP concentrations of 76 micrograms ml-1, the 45-2D9-HP conjugate resulted in significantly more long-term cures of PDT treated flank tumours compared with free HP at the same concentration. 45-2D9 alone had no effect on tumour growth. The antibody-HP conjugate resulted in significantly less local toxicity compared with standard Photofrin II PDT, and also achieved a greater number of long-term cures. This 'photoimmunotherapy' demonstrates the ability to treat established tumours with greater efficacy and decreased morbidity, probably due to specific sensitizer targetting which allows normal surrounding tissue to be spared upon illumination.
Pogrebniak
H W
HW
Thoracic Oncology Section, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892.
Matthews
W
W
Black
C
C
Russo
A
A
Mitchell
J B
JB
Smith
P
P
Roth
J A
JA
Pass
H I
HI
D016475:3T3 Cells; D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D017323:Dihematoporphyrin Ether / Q000627:therapeutic use* / Q000633:toxicity; D006415:Hematoporphyrins / Q000032:analysis; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009132:Muscles / Q000737:chemistry; D009374:Neoplasms, Experimental / Q000737:chemistry / Q000188:drug therapy*; D010778:Photochemotherapy; D012867:Skin / Q000737:chemistry; D016896:Treatment Outcome
D000911:Antibodies, Monoclonal; D006415:Hematoporphyrins; D017323:Dihematoporphyrin Ether