Cooperative effect of radioimmunotherapy and antiangiogenic therapy with thalidomide in human cancer xenografts.
Antiangiogenic therapy may prolong the dormancy of cancer lesions. Moreover, radioimmunotherapy (RIT) may eradicate this population of cells. This study dealt with determining the benefits associated with the combined usefulness of these 2 therapies with respect to inhibition of tumor growth.


METHODS
Antiangiogenic therapy using oral thalidomide (daily dose, 200 mg/kg) and RIT involving a single intravenous injection (4.63 MBq (131)I-A7, an IgG1 murine monoclonal antibody) were conducted in mice bearing LS180 human colon cancer xenografts. RIT with an irrelevant IgG1, HPMS-1, was also performed as a control. Antiangiogenesis of thalidomide was investigated by immunohistochemical analysis of tumor sections.


RESULTS
Antiangiogenic therapy and RIT with (131)I-A7 significantly suppressed the growth of xenografts. This combination produced more efficient tumor growth inhibition than did the monotherapy (P < 0.005). RIT using (131)I-HPMS-1 was far less effective than (131)I-A7, even when combined with thalidomide administration. Immunohistochemistry revealed a decrease in the microvessel number within tumors treated with thalidomide (P < 0.0001). Combined therapy further reduced the microvessel number (P < 0.01 vs. thalidomide monotherapy).


CONCLUSIONS
The combination of RIT and thalidomide antiangiogenic therapy produces a better response of tumors than does monotherapy. Acting in concert, antiangiogenic therapy may prolong the dormancy of cancer lesions and RIT may eradicate this population of cells.
Kinuya
Seigo
S
Department of Biotracer Medicine, Kanazawa University Graduate School of Medical Sciences, Japan. kinuya@med.kanazawa-u.ac.jp
Kawashima
Atsuhiro
A
Yokoyama
Kunihiko
K
Koshida
Kiyoshi
K
Konishi
Shota
S
Watanabe
Naoto
N
Shuke
Noriyuki
N
Bunko
Hisashi
H
Michigishi
Takatoshi
T
Tonami
Norihisa
N
D020533:Angiogenesis Inhibitors / Q000627:therapeutic use*; D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D003110:Colonic Neoplasms / Q000628:therapy*; D005260:Female; D006801:Humans; D007457:Iodine Radioisotopes; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D016499:Radioimmunotherapy; D013792:Thalidomide / Q000627:therapeutic use*; D013997:Time Factors; D014183:Transplantation, Heterologous
D020533:Angiogenesis Inhibitors; D000911:Antibodies, Monoclonal; D007457:Iodine Radioisotopes; D013792:Thalidomide