title: Adoptive immunotherapy involving recombinant human M-CSF and R24 anti-melanoma antibody induces human T-cell infiltration into human melanoma xenografts.
abstract: Directed motion toward and infiltration of tumor masses by effector cells is essential for successful adoptive immunotherapy. A human/SCID mouse chimeric system was used to examine whether an antitumor antibody and recombinant human monocyte colony-stimulating factor (rhM-CSF) could promote human T-cell infiltration of a human tumor in vivo. Fourteen days after subcutaneous injection of the human melanoma cell line M-14 into SCID recipients, several adoptive immunotherapy regimens were initiated using activated human T cells, an anti-melanoma monoclonal antibody (MoAb) (R24), and rhM-CSF. Effects on tumor growth and human T-cell infiltration into the tumor were assessed. Compared with other treatment groups, only mice treated with the combination of activated human T cells, anti-tumor MoAb, and rhM-CSF demonstrated a significant cellular infiltrate in the melanoma. Immunohistology demonstrated human T cells present in the tumor up to 7 days after injection. Groups treated with rhRANTES or rmGM-CSF in place of rhM-CSF exhibited markedly less human T-cell infiltration. Additionally, only mice treated with human T cells, R24, and rhM-CSF demonstrated a significant antitumor response in vivo. This model suggests that activated human T cells can be specifically targeted to in vivo tumor sites by combined treatment with an antitumor antibody and rhM-CSF.
authors.affiliation: Laboratory of Experimental Immunology, SAIC Frederick, MD 21702, USA.
authors.forename: K C
authors.initials: KC
authors.lastname: Conlon
authors.forename: M R
authors.initials: MR
authors.lastname: Anver
authors.forename: D L
authors.initials: DL
authors.lastname: Longo
authors.forename: J R
authors.initials: JR
authors.lastname: Ortaldo
authors.forename: W J
authors.initials: WJ
authors.lastname: Murphy
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology* / Q000627:therapeutic use*; D002634:Chemotaxis, Leukocyte / Q000276:immunology*; D006801:Humans; D016219:Immunotherapy, Adoptive / Q000379:methods*; D016173:Macrophage Colony-Stimulating Factor / Q000627:therapeutic use*; D008545:Melanoma / Q000276:immunology* / Q000628:therapy*; D051379:Mice; D016513:Mice, SCID; D009368:Neoplasm Transplantation / Q000276:immunology; D012878:Skin Neoplasms / Q000276:immunology / Q000628:therapy; D013601:T-Lymphocytes / Q000276:immunology*; D014183:Transplantation, Heterologous / Q000276:immunology*; D014407:Tumor Cells, Cultured
chemical_list: D000911:Antibodies, Monoclonal; D016173:Macrophage Colony-Stimulating Factor