TY - JOUR
T1 - Pulmonary metastases neutralization and tumor rejection by in vivo administration of β glucan and bispecific antibody
AU - Penna, Christophe
AU - Dean, Phillip A.
AU - Nelson, Heidi
PY - 1996/1/26
Y1 - 1996/1/26
N2 - Bispecific antibody (BsAb) with specificity for tumor cell surface antigen and the CD3 molecule on T cells can redirect activated T cells to lyse tumor cells. Since the ex vivo expansion and activation of T cells is impractical and ineffective for treating established tumors, we tested whether the immune stimulant β glucan could in situ-activate T cells, which could secondarily be retargeted with BsAbs to lyse tumor cells. To test for tumor neutralization, C3H/HeN mice were injected i.v. with C1-62 melanoma cells and immediately treated with i.p. β glucan and/or anti-CD3 (500AZ) x anti p97 (96.5) F(ab')2 BsAb i.v. Pulmonary metastases were counted 14 days later. To test for tumor rejection and survival in a solid tumor model, mice were injected s.c. and i.p. with C1-62 cells and 7 days later administered β glucan i.p. and/or F(ab')2 BsAb i.v. In the neutralization model, there was a significant reduction in the number of metastases in the β glucan + BsAb group, as compared with controls, and with β glucan alone. In the established tumor model, β glucan + BsAb reduced the incidence of s.c. tumors as compared with control, with BsAb alone and with β glucan alone. It also prolonged survival of tumor-bearing mice compared with control, BsAb alone and β glucan alone. We conclude that T cells can be activated in vivo by β glucan and retargeted with F(ab')2 BsAb.
AB - Bispecific antibody (BsAb) with specificity for tumor cell surface antigen and the CD3 molecule on T cells can redirect activated T cells to lyse tumor cells. Since the ex vivo expansion and activation of T cells is impractical and ineffective for treating established tumors, we tested whether the immune stimulant β glucan could in situ-activate T cells, which could secondarily be retargeted with BsAbs to lyse tumor cells. To test for tumor neutralization, C3H/HeN mice were injected i.v. with C1-62 melanoma cells and immediately treated with i.p. β glucan and/or anti-CD3 (500AZ) x anti p97 (96.5) F(ab')2 BsAb i.v. Pulmonary metastases were counted 14 days later. To test for tumor rejection and survival in a solid tumor model, mice were injected s.c. and i.p. with C1-62 cells and 7 days later administered β glucan i.p. and/or F(ab')2 BsAb i.v. In the neutralization model, there was a significant reduction in the number of metastases in the β glucan + BsAb group, as compared with controls, and with β glucan alone. In the established tumor model, β glucan + BsAb reduced the incidence of s.c. tumors as compared with control, with BsAb alone and with β glucan alone. It also prolonged survival of tumor-bearing mice compared with control, BsAb alone and β glucan alone. We conclude that T cells can be activated in vivo by β glucan and retargeted with F(ab')2 BsAb.
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U2 - 10.1002/(SICI)1097-0215(19960126)65:3<377::AID-IJC17>3.0.CO;2-7
DO - 10.1002/(SICI)1097-0215(19960126)65:3<377::AID-IJC17>3.0.CO;2-7
M3 - Article
C2 - 8575861
AN - SCOPUS:0030044851
SN - 0020-7136
VL - 65
SP - 377
EP - 382
JO - International Journal of Cancer
JF - International Journal of Cancer
IS - 3
ER -