Divergent effects of 4-1BB antibodies on antitumor immunity and on tumor-reactive T-cell generation.

摘要: 4-1BB is an inducible receptor-like protein expressed rapidly by both CD4 and CD8 T-cells after activation. cross-linking, either binding to 4-1BBL or antibody ligation, delivers a costimulatory signal enhance T-cell activation proliferation. Previous studies have demonstrated that the administration of monoclonal antibodies (mAbs) induces antitumor immune responses. In current study using several murine tumors, we examined systemic effects mAb on growth s.c., intracranial (i.c.), pulmonary metastases. addition, generation effector T cells were examined. Treatment 3-day i.c. MCA 205 sarcoma GL261 glioma with resulted in prolongation survival cure disease some mice, whereas only minimal therapeutic observed established s.c. tumors. No against poorly immunogenic B16/D5 melanoma observed. Interestingly, successful treatment tumors induced concomitant regression Experiments severe combined immunodeficient mice depleted dependence effects. For tumor-draining lymph nodes (LNs), had adverse effects, despite apparent hypertrophy LNs. During vitro LN anti-CD3 interleukin 2, augmented proliferation, resulting increase cells. However, they less than not treated adoptive immunotherapy, coadministration enhanced efficacy. These results thus demonstrate limits potential advantages interactions vivo suggest may be used variety immunotherapeutic approaches.