The therapeutic efficacy of angiostatin against weakly- and highly-immunogenic 3LL tumors.
BACKGROUND
Antiagiogenesis represents a promising approach to cancer therapy. We have previously demonstrated that the antitumor effects of endostatin, one of the most potent angiostatic agents, could be enhanced when combined with immunotherapy. Our current study evaluated whether anti-tumor immune response could also potentiate the therapuetic efficacy of another antiangiogenic drug, angiostatin.


RESULTS
Using Matrigel assay, we showed that our preparation of recombinant angiostatin possessed potent anti-angiogenic activity in vivo. The antitumor effects of recombinant angiostatin were tested against weakly-immunogenic 3LL Lewis lung carcinoma versus its highly immunogenic variant 3LL-C75. We showed that angiostatin inhibited the growth of 3LL-C75 more potently than that of 3LL tumor, suggesting that the host's immune response potentiates the antitumor effects of angiostatin. This conclusion was further supported by the finding that the antitumor activity of angiostatin against 3LL-C75 tumor was lower in immunodeficient nude mice in comparison with immunocompetent mice. Immunization of C57BL/6 mice with 3LL-C75 cells stimulated the antitumor immunity and inhibited the growth of parental 3LL tumor. Angiostatin treatment of immunized mice further enhanced the antitumor effect of tumor vaccination.


CONCLUSIONS
Antitumor immune response could complement the therapeutic efficacy of angiostatin.
Li
Mengfeng
M
Department of Pathology, University of Pittsburgh, University of Pittsburgh Cancer Institute, Pittsburgh, PA 15123, USA.
Huang
Xiaojun
X
Zhu
Zhenyu
Z
Zhao
Qun
Q
Wong
Michael
M
Gorelik
Elieser
E
D020533:Angiogenesis Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D043168:Angiostatins; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D019496:Cancer Vaccines / Q000276:immunology; D018827:Carcinoma, Lewis Lung / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D003094:Collagen / Q000494:pharmacology; D004338:Drug Combinations; D004357:Drug Synergism; D043169:Endostatins; D005260:Female; D016867:Immunocompromised Host; D016233:Immunotherapy, Active; D007797:Laminin; D051379:Mice; D008810:Mice, Inbred C57BL; D008819:Mice, Nude; D009389:Neovascularization, Pathologic / Q000188:drug therapy / Q000473:pathology; D018919:Neovascularization, Physiologic / Q000187:drug effects; D010446:Peptide Fragments / Q000494:pharmacology / Q000627:therapeutic use*; D010958:Plasminogen / Q000494:pharmacology / Q000627:therapeutic use*; D011509:Proteoglycans; D011994:Recombinant Proteins / Q000627:therapeutic use
D020533:Angiogenesis Inhibitors; D000970:Antineoplastic Agents; D019496:Cancer Vaccines; D004338:Drug Combinations; D043169:Endostatins; D007797:Laminin; D010446:Peptide Fragments; D011509:Proteoglycans; D011994:Recombinant Proteins; C059485:matrigel; D043168:Angiostatins; D010958:Plasminogen; D003094:Collagen