1. ¹Department of Neurosurgery, Rush University Medical Center, John H Stroger Hospital of Cook County, Chicago, Illinois, USA
2. ²Hektoen Institute for Medical Research, Chicago, Illinois, USA
3. ³Department of Microbiology and Immunology, University of Illinois at Chicago, Chicago, Illinois, USA

Correspondence: Dr Terry Lichtor, MD, PhD, Department of Neurosurgery, 1900 West Polk Street, Chicago, IL 60612, USA. E-mail: Terry_Lichtor@rush.edu

Received 24 August 2004; Published online 1 April 2005.

Abstract

Prior studies have revealed the immunotherapeutic properties of a vaccine prepared by transfer of genomic DNA from breast cancer cells into a highly immunogenic cell line. The rationale for this type of vaccine is that genes specifying an array of weakly immunogenic, unique tumor antigens associated with the malignant cells will be expressed in a highly immunogenic form by the transfected cells. Here, the immunotherapeutic properties of a vaccine prepared by transfection of mouse fibroblasts with DNA from a breast carcinoma (SB-5b) that arose spontaneously in a C3H/He mouse (H-2K^b) were tested in mice with intracerebral breast cancer. To augment their nonspecific immunogenic properties, before DNA transfer, the fibroblasts (of C3H/He mouse origin) were modified to express allogeneic MHC class I H-2K^b-determinants and to secrete IL-2, IL-18 or GM-CSF. The results indicate that C3H/He mice injected intracerebrally (i.c.) with the breast cancer cells and syngeneic/allogeneic-transfected fibroblasts modified to secrete IL-2 survived significantly longer (P<.005) than mice in various control groups, including mice injected i.c. with the breast cancer cells alone. The immunotherapeutic properties of transfected fibroblasts modified to secrete IL-18 or GM-CSF were less efficacious. The results of two independent in vitro cytotoxicity assays indicate that systemic cellular antitumor immunity was generated in mice injected i.c. with the transfected cells, and the immunity was mediated predominantly by CD8⁺ T cells.