PULMONARY METASTASES NEUTRALIZATION AND TUMOR REJECTION BY IN-VIVO ADMINISTRATION OF BETA-GLUCAN AND BISPECIFIC ANTIBODY

Bispecific antibody (BsAb) with specificity for tumor cell surface ant igen 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 cel ls is impractical and ineffective for treating established tumors, we tested whether the immune stimulant beta glucan could in situ-activate T cells, which could secondarily be retargeted with BsAbs to lyse tum or cells. To test for tumor neutralization, C3H/HeN mice were injected i.v. with Cl-62 melanoma cells and immediately treated with i.p. B gl ucan and/or anti-CD3 (500A2) x anti-p97 (96.5) F(ab')(2) BsAb i.v. Pul monary metastases were counted 14 days later. To test for tumor reject ion and survival in a solid tumor model, mice were injected s.c. and i .p. with Cl-62 cells and 7 days later administered B glucan i.p. and/o r F(ab')(2) BsAb i.v. In the neutralization model,there was a signific ant reduction in the number of metastases in the beta glucan + BsAb gr oup, as compared with controls, and with B glucan alone. In the establ ished tumor model, beta glucan + BsAb reduced the incidence of s.c. tu mors as compared with control, with BsAb alone and with beta glucan al one. It also prolonged survival of tumor-bearing mice compared with co ntrol, BsAb alone and beta glucan alone. We conclude that T cells can be activated in vivo by beta glucan and retargeted with F(ab')(2) BsAb . (C) 1996 Wiley-Liss, Inc.