The goals of this laboratory are to understand the immunology of the brain and to develop alternative therapies, including gene- and immuno-therapeutic approaches for treating patients with high-grade primary brain tumors. We use glioma cell culture as a model system in addition to several rat glioma models. Based upon the efficacy and lack of toxicity obtained in the in vitro and in vivo model systems, we translated the findings into several Phase I clinical trials, one of which used autologous, Interleukin-2 and lectin-stimulated lymphocytes and another which used alloreactive cytotoxic T lymphocytes for cellular therapy of recurrent gliomas. We examined the use of another allogeneic T cell effector line, TALL-104, for adoptive immunotherapy. We studied the trafficking of ex-vivo activated lymphocytes when placed intracranially. We also tested the role of NCAM in tumor cell invasion and the effects of cytokines on MHC and ICAM-1 expression by gliomas. Various combinations of cytokine and suicide gene therapy plus or minus adoptive immunotherapy were explored in the rat glioma models. We also have tested integrin antagonists, chimeric proapoptotic ribozymes and ribozymes to a cell cycle target in rat glioma models or in a rabbit eye model of proliferative vitreoretinopathy. Current projects involve the creation and characterization of immunotherapy resistant glioma models, and the antigen presenting capability of microglia after their interaction with alloreactive CTL damaged glioma.

1. Kruse, C.A., Rubinstein, D. (2001) Cytotoxic T Lymphocytes Reactive to Patient Major Histocompatibility Proteins for Therapy of Recurrent Primary Brain Tumors, in Brain Tumor Immunotherapy, eds. D. Bigner, D.P. Becker, T.F. Cloughsey, and L.M. Liau, Humana Press, pp 149-170.
2. Kruse, C.A., Visonneau, S., Kleinschmidt-DeMasters, B.K., Gup, C.J., Gomez, G.G., Paul, D.B., Santoli, D. (2000) A Human Leukemic T Cell Line, TALL-104, is Cytotoxic to Human Malignant Brain Tumors and Traffics Through Brain Tissue: Implications for Local Adoptive Immunotherapy, Cancer Research 60, 5731-5739.
3. Owens, G.C., Orr, E.A., Kleinschmidt-DeMasters, B.K., Muschel, R.J., Berens, M.E., Kruse, C.A. (1998) Overexpression of a transmembrane isoform of neural cell adhesion molecule (NCAM) alters the invasiveness of rat CNS-1 glioma, Cancer Research 58, 2020-2028.
4. Kruse, C.A., Lamb, C., Hogan, S., Smiley, WR, Kleinschmidt-DeMasters, B.K., Burrows, F.J. (2000) Purified Herpes simplex thymidine kinase retroviral particles. II. Influence of clinical parameters and bystander killing mechanisms, Cancer Gene Therapy 7, 118-127.
5. Burrows, F.B., Gore, M., Smiley, W.R., Kanemitsu, M.Y., Jolly, D.R., Read, S.B., Nicholas, T., Kruse, CA. (2002) Purified Herpes simplex thymidine kinase retroviral particles. III. Characterization of bystander killing mechanisms in transfected tumor cells, Cancer Gene Therapy 9, 87-95.
6. Paul, D.B., Read, S.B., Kulprathipanja, N., Gomez, G.G., Kleinschmidt-DeMasters, B.K., Schiltz, P.M., Kruse, C.A. (2003) gInterferon Transduced 9L Gliosarcoma: Cytokine Gene Therapy and its Relevance to Cellular Therapy with Alloreactive Cytotoxic T Lymphocytes, J. Neuro-Oncol. 64, 89-99.
   
7. Nicholas, T.W., Read, S.B., Burrows, F.J., Kruse, C.A. (2003) Suicide gene therapy with Herpes simplex virus thymidine kinase and ganciclovir is enhanced with connexins to improve gap junctions and bystander effects, Histol. Histopathol. 18, 509-517.
8. Read, S.B., Kulprathipanja, N., Gomez, G.G., Paul, D.B., Winston, K.R., Robbins, J.M., Kruse, C.A. (2003) Human alloreactive cytotoxic T lymphocytes interactions with gliomas, and with those having upregulated HLA expression from exogenous IFNg or IFNg gene modification, J. Int. Cyt. Res. 23, 391-405.
9. Mandava, N., Paul, D.B., Blackburn, P., Wilson, M.W., Alspaugh, E.B., Whiting, C., Barber, J.R., Robbins, J.M., Kruse, C.A. (2002) Chimeric ribozyme to proliferating cell nuclear antigen reduces the severity of proliferative vitreoretinopathy in a rabbit model, Invest. Opthalmol. Visual Sci. 43, 3338-3348.