Study of photodynamic efficiency of the hematoporphyrin conjugated with antibody to VEGF in mouse Lewis carcinoma.
OBJECTIVE
To examine photodynamic antitumor and anti-metastatic effect of hematoporphyrin, conjugated with antibodies to VEGF in comparison with native hematoporphyrin in experiments with high metastatic, angiogenesis-independent Lewis carcinoma (LLC) and its low metastatic angiogenesis-dependent variant - LLC/R9.


METHODS
Mice with LLC or with LLC/R9 were treated by photodynamic therapy (PDT) using new photosensitizer - hematoporphyrin conjugated with antibodies to VEGF, in comparison with hematoporphyrin or aminolevulinic acid. Tumor growth indices and metastasis incidence were calculated.


RESULTS
Strong antitumor effect of PDT with new conjugate was demonstrated - delay of tumor development by 70% whereas native hematoporphyrin with the same treatment regime did not show any significant effect. Most pronounced effect of conjugate was demonstrated on the growth and metastasing of LLC/R9, which was characterized by the resistance to chemotherapeutic drugs. Slowdown of the tumor growth - up to complete regression - was detected already at the third day after PDT and, on the average was about 70% of control values. Non-conjugated hematoporphyrin under parameters chosen did not cause antitumor effect. Metastases calculation demonstrated that total metastatic volume reduced by seven times in conjugate group and by 3.5 times in hematoporphyrin group.


CONCLUSIONS
Hematoporhyrin conjugate studied had high photodynamic antitumor activity. Taking into consideration substantial prevalence in clinical practice of drug-resistant tumors and angiogenesis-dependent character of metastasis process, further study and application of photosensitizers, conjugated with antibodies to VEGF, may help to improve the clinical outcomes.
Novichenko
N L
NL
R.E. Kavetsky Institute of Experimental Pathology, Oncology and Radiobiology of the National Academy of Sciences of Ukraine, Kiev 03022, Ukraine. neura@mail.ru
Mamchur
A A
AA
Lisniak
I O
IO
Gamaliya
M F
MF
D000818:Animals; D000906:Antibodies / Q000627:therapeutic use*; D018827:Carcinoma, Lewis Lung / Q000188:drug therapy*; D006415:Hematoporphyrins / Q000627:therapeutic use*; D051379:Mice; D010778:Photochemotherapy / Q000379:methods*; D017319:Photosensitizing Agents / Q000627:therapeutic use*; D042461:Vascular Endothelial Growth Factor A / Q000276:immunology* / Q000627:therapeutic use
D000906:Antibodies; D006415:Hematoporphyrins; D017319:Photosensitizing Agents; D042461:Vascular Endothelial Growth Factor A