Recombinant gp100 protein presented by dendritic cells elicits a T-helper-cell response in vitro and in vivo

Induction of a helper T (TH)-cell response is a critical element in the gen eration of anti-tumor immunity. The majority of immunotherapeutic approache s have so far been concerned with the generation of cytotoxic T lymphocytes (CTLs). This also accounts for gp100, a melanoma-associated protein which induces a potent CTL response. Because of the high immunogenicity of gp100, we considered it of special interest to explore the feasibility of generat ing gp100 specific TH cells. Human dendritic cells (DCs) were loaded with r ecombinant gp100 protein, and the response of autologous TH cells was evalu ated in vitro and in vivo. We have observed that gp100 peptides can be pres ented by DCs of certain MHC class II haplotypes, which led to proliferation and cytokine production of TH-1 cells in vitro. Furthermore, transfer of g p100 protein-loaded human DCs into SCID mice also induced proliferation of autologous, unprimed peripheral blood leukocytes (PBLs) and selective expan sion of TH cells. When human T cells from the spleen of SCID mice were reco vered and restimulated in vitro, they strongly proliferated in response to gp100-loaded DCs, while showing minimal proliferative activity in response to DCs loaded with a control antigen. Thus, it is possible to induce an eff icient MHC class II-restricted TH response by in vitro stimulation or in vi vo vaccination with DCs which have been loaded with a purified tumor-associ ated antigen. Int. J. Cancer 83:547-554, 1999. (C) 1999 Wiley-Liss, Inc.