ADOPTIVE IMMUNOTHERAPY OF CANCER USING MONOCYTE-DERIVED MACROPHAGES -RATIONALE, CURRENT STATUS, AND PERSPECTIVES

Adoptive transfer of host defense cells may be able to correct an othe rwise defective generation of competent immune cells in patients with cancer. Ex vivo-grown cytotoxic macrophages (MAC) able to recognize an d destroy tumor cells but not normal cells are effective in murine mod els of metastasizing tumors. After the development of large-scale tech nology to generate MAC in vitro from blood monocytes (MO), clinical tr ials in cancer patients have proven the feasibility and safety of infu sing >3 x 10(9) autologous MO-derived MAC activated by interferon-gamm a or Lipopolysaccharide. Various modalities of adoptive immunotherapy with human MAC have been realized: routes of application used were int ravenous, intraperitoneal, intrapleural, and through selective hepatic artery perfusion, In addition, MAC have been generated from MO collec ted after granulyte-macrophage colony-stimulating factor treatment in vivo. Biodistribution studies using (111)indium-labeled cells have rev ealed localization of MAC to sites of bulk tumor growth on regional in fusion as well as to Liver metastases on systemic application. Maligna nt ascites disappeared in about 50% of patients after intraperitoneal treatment, yet no other evidence of therapeutic efficacy of MAC could be demonstrated, Further advances of adoptive transfer of MO-derived c ells are developed with emphasis on the generation of antigen-presenti ng cells primed in vitro with tumor cells or specific peptides.