title: Pulmonary metastases neutralization and tumor rejection by in vivo administration of beta glucan and bispecific antibody.
abstract: 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 beta 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 Cl-62 melanoma cells and immediately treated with i.p. beta glucan and/or anti-CD3 (500A2) 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 Cl-62 cells and 7 days later administered beta 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 beta glucan + BsAb group, as compared with controls, and with beta glucan alone. In the established tumor model, beta glucan + BsAb reduced the incidence of s.c. tumors as compared with control, with BsAb alone and with beta glucan alone. It also prolonged survival of tumor-bearing mice compared with control, 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.
authors.affiliation: Department of Surgery, Mayo Clinic, Rochester, MN 55905, USA.
authors.forename: C
authors.initials: C
authors.lastname: Penna
authors.forename: P A
authors.initials: PA
authors.lastname: Dean
authors.forename: H
authors.initials: H
authors.lastname: Nelson
mesh_terms: D000276:Adjuvants, Immunologic / Q000627:therapeutic use*; D000818:Animals; D018033:Antibodies, Bispecific / Q000627:therapeutic use*; D000951:Antigens, Neoplasm / Q000276:immunology; D017252:CD3 Complex / Q000276:immunology; D005260:Female; D005936:Glucans / Q000627:therapeutic use*; D008175:Lung Neoplasms / Q000276:immunology / Q000556:secondary / Q000628:therapy*; D008213:Lymphocyte Activation / Q000187:drug effects; D008545:Melanoma / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D013601:T-Lymphocytes / Q000276:immunology* / Q000473:pathology
chemical_list: D000276:Adjuvants, Immunologic; D018033:Antibodies, Bispecific; D000951:Antigens, Neoplasm; D017252:CD3 Complex; D005936:Glucans