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.