Cancer Therapy Vol 4, page 163 Cancer Therapy Vol 4, 163-170, 2006
Advantages of a unique DNA-based vaccine in comparison to paclitaxel in treatment of an established intracerebral breast cancer in mice Research Article
Terry Lichtor1, Roberta P Glick1, Henry Lin1, Amla Chopra2, InSug O-Sullivan2 and Edward P Cohen2 1 2
Department of Neurological Surgery, Rush University Medical Center and John H Stroger Hospital of Cook County Department of Microbiology and Immunology, University of Illinois at Chicago; Chicago, Illinois
__________________________________________________________________________________ *Correspondence: Terry Lichtor, MD, PhD, Department of Neurosurgery, Rush University Medical Center, 1900 West Polk Street, Chicago, Illinois 60612, Telephone: 312-864-5120, Fax: 312-864-9606, E-Mail: Terry_Lichtor@rush.edu Key words: DNA-Based Vaccine, IL-2, breast cancer, intracerebral cannula Abbreviations: Intracerebrally, (i.c.); intraperitoneal, (i.p.); tumor associated antigens, (TAA)
This work was supported by a grant from the CINN Foundation awarded to Drs Lichtor and Glick, and by NIDCR grant number 1 RO1 DEO13970-01A2 awarded to Dr. Cohen.
Received: 19 April 2006; Accepted: 03 May 2006; electronically published: May 2006
Summary In this study we compared the benefits of treating C3H/He mice with an established intracerebral breast carcinoma by immunization with a unique DNA-based vaccine to chemotherapy with paclitaxel. Prior studies revealed the immunotherapeutic properties of a vaccine prepared by transfer of genomic DNA from breast cancer cells into a highly immunogenic cell line. Here, C3H/He mice with an established intracerebral breast cancer were treated either by injection into the tumor bed through a unique cannula system with the cell based vaccine or with paclitaxel administered intraperitoneally. Both treatment strategies were effective in prolonging survival and stimulating a systemic anti-tumor immune response (p< 0.025). However, unlike mice treated with the vaccine, the animals that received paclitaxel alone displayed significant toxic side effects. No additional therapeutic advantage was detected when these two treatment strategies were combined. The vaccine tended to provide a somewhat better therapeutic and clearly better systemic immunologic effect based on two independent spleen cell assays in comparison to paclitaxel.
from an adenocarcinoma of the breast into a highly immunogenic mouse fibroblast cell line. The cells used as DNA-recipients were modified in advance of DNAtransfer to secrete various immune-augmenting cytokines. The rationale was that genes specifying tumor associated antigens (TAA) would be expressed in a highly immunogenic form by the transfected cells. As the transferred DNA is integrated into the genome of the recipient cells, and replicated as the cells divide, the vaccine could be prepared with DNA derived from microgram amounts of tumor tissue. It is likely that the multiple mutant and/or dysregulated genes in the breast cancer cells specifying an array of unidentified weakly immunogenic tumor associated antigens were expressed in a highly immunogenic form by the transfected cells. Since
I. Introduction We recently reported on the immunotherapeutic properties of a unique DNA-based cell vaccine for treatment of intracerebral (i.c.) breast cancer in C3H/He mice (Lichtor et al, 2005). In particular we showed that C3H/He mice injected with a cell mixture containing a breast carcinoma (SB5b) along with a vaccine prepared by transfection of mouse fibroblasts with DNA from the breast carcinoma (SB5b) survived longer than mice in various control groups. Systemic cellular tumor immunity was generated in the mice injected intracerebrally with the transfected cells, which was mediated predominantly by CD8+ T cells (Lichtor et al, 2005). The vaccine was prepared by transfer of sheared genomic DNA-fragments
163