EDUCATION

Degrees

• B.S. – Colorado State University – 1976
• M.S. – Colorado State University – 1977
• Ph.D. – UCLA – 1980

Postdoctoral Training

• UCLA, Los Angeles, CA
• Caltech, Pasadena, CA
• University of Colorado Health Sciences Center, Denver, CO

Faculty Appointments

• University of Colorado Health Sciences Center, Denver, CO
• La Jolla Institute for Molecular Medicine, San Diego, CA
• Sidney Kimmel Cancer Center, San Diego, CA
• Burnham Institute for Medical Research, San Diego, CA
• University of California, Los Angeles, LA, CA

RESEARCH AREA

The goals of this laboratory are directed toward an understanding of the immunology of the brain and immunoresistance mechanisms used by tumor cells that will allow development of alternative therapies for treating patients with primary malignant brain tumors. We use glioma cell culture as a model system, in addition to syngeneic mouse and rat or human xenograft brain tumor models.

Current basic research projects involve: 1) the development of algorithms that allow selection of allodonors to obtain robust alloreactive cytotoxic T lymphocytes (CTL) following one-way mixed lymphocyte reactions (MLR) based upon molecular HLA mismatch of responder:stimulator pairs, 2) enhancing generation of immunotherapeutic CTL using dendritic cells (DC) for one-way lymphocyte DC reactions, where the DC have been differentially activated using pathogen associated signaling molecules (CLR or PRR agonists) contained with nanoparticles such that they better kill tumor and cancer stem cells, and 3) use of allogeneic glioma cell lines as sources of tumor associated antigens, which can be the target of tumor cell or dendritic cell vaccines.

Other translational research studies are focused on combining innovative cellular and gene therapy approaches. A dose escalation Phase I clinical trial involving intratumoral adoptive transfer of alloreactive CTL is underway. As well, we are engineering alloreactive CTL as vector producing cells. Alloreactive CTL that possess the capability of trafficking through tissues as part of their immune surveillance function will be used to deliver replication competent retroviruses within the brain to reach the infiltrating tumor cells. The retroviral vectors will code for suicide genes such that when prodrug is administered, the transduced tumor cells will die. We are exploring this multi-modal therapy not only for primary malignant brain tumors, but for tumors metastatic to brain.

GRANTS

• NIH/NCI R01 CA125244-01A2 (Kruse/Liau PIs) 07/01/10 – 06/30/15
  Title: “Adoptive Transfer of AlloCTL for Immunotherapy of Recurrent Gliomas”
  This grant supports a dose escalation Phase I clinical study using intratumoral alloreactive CTL for recurrent glioma patients. Up to ten alloCTL infusates are placed over a ten month period into the resected tumor beds. Standard follow-up entails neuroimaging and neurologic status, as well as monitoring for the development of an endogenous immune response to the immune therapy.
• NIH/NCI R01CA154256 (Kruse/Minev) 07/01/10 – 06/30/15
  “Optimizing Induction Conditions for Immunotherapeutic CTL”
  For this grant dendritic cell activation is modulated with pathogen associated signaling molecules contained with nanoparticles.  The differentially-activated dendritic cells will then be used to stimulate naïve T cells into effector CTL. The generated CTL will be functionally and phenotypically characterized in vitro and in vivo using mouse glioma cell targets or those enriched for brain tumor stem cells in culture.

LINKS

PUBLICATIONS (recent articles)

1. Gomez, G.G., Varella-Garcia, M.-L., Kruse, C.A. (2006) Isolation of Immunoresistant Human Glioma Cell Clones after Immunoselection with Alloreactive Cytotoxic T Lymphocytes: Cytogenetic and Molecular Cytogenetic Characterization. Cancer Genetics Cytogenetics, 165, 121-134.
2. Gomez, G.G., Kruse, C.A. (2007) Functional and Cellular Characterization of Immunoresistant Human Glioma Cell Clones Selected with Alloreactive Cytotoxic T Lymphocytes Reveals Their Upregulated Synthesis of Biologically Active TFG-, J. Immunother., 30, 261-273.
3. Zhang, J.G., Eguchi, J., Kruse, C.A., Gomez, G.G., Fakhrai, H., Schroter, S., Ma, W., Hoa, N., Minev, B., Delgado, C., Wepsic, H.T., Okada, H., Jadus, M.R. (2007) Antigenic profiles of human gliomas: Implications for patient CTL targeting of tumor associated antigens with allogeneic tumor cell-based vaccines or dendritic-cell based therapies. Clin. Cancer Res. 13, 566-575.
4. Gomez, G.G., Hickey, M.J., Tritz, R., Kruse, C.A. (2008) Immunoresistant Human Glioma Cell Clones Selected with Alloreactive Cytotoxic T Lymphocytes: Downregulation of Multiple Proapoptotic Factors, Gene Ther. Molc. Biol. 12, 101-110.
5. Zhang, J.G., Kruse, C.A., Driggers, L., Hoa, N., Wisoff, J., Allen, J.C., Zagzag, D., Newcomb, E.W., Jadus, M.R. (2008) Tumor antigen precursor protein (TAPP) profiles of adult and pediatric brain tumors identify potential targets for immunotherapy, J. NeuroOncol. 88, 65-76. DOI 10.1007/s11060-008-9534-4.
6. Tritz, R., Mueller, B.M., Hickey, M.J., Lin, A.H., Gomez, G.G., Hadwiger, P., Sah, D.W.Y., Muldoon, L., Neuwelt, E.A., Kruse, C.A. (2008) siRNA Downregulation of the PATZ1 gene in human glioma cells increases their sensitivity to apoptotic stimuli. Cancer Therapy 6, 865-876.
7. Tritz, R., Hickey, M.J., Lin, A.H., Hadwiger, P., Sah, D.W.Y., Neuwelt, E.A., Mueller, B.M., Kruse, C.A. (2009) FAPP2 Gene Downregulation Increases Tumor Cell Sensitivity to Fas-Induced Apoptosis, Biochem. Biophys. Res. Commun. 383, 167-171. Doi:10.1016/j.bbrc.2009.03.126.
8. Hickey, M.J., Malone, C.C., Erickson, K.L., Jadus, M.R., Prins, R.M., Liau, L.M., Kruse, C.A. (2010) Cellular and Vaccine Therapies for Gliomas, J. Transl. Med. 8, 100-108.
9. Haga, K., Lin, A., Hickey, M.J., Gomez, G.G., Logg, C.R., Kimura, T., Hiraoka, K., Matsumoto, H., Ohno, I., Kruse, C.A., Kasahara, N. (2010) Combined Cellular Therapy with Alloreactive Cytotoxic T Lymphocytes and Prodrug Activator Gene Therapy with Replicating Retrovirus Vectors in a Brain Tumor Model, Mol. Therapy, submitted.
10. 10. Stathopoulos, A., Pretto, C., Devilliers, L., Pierre, D., Hofman, F.M., Kruse, C.A., Jadus, M., Chen, T.C., Schijns, V.E.J.C. (2011) Development of immune memory cells against glioma tumor after tumor regression by immunotherapeutic Toll-like receptor 7/8 activation. OncoImmunology 1:3, 1-8.
11. 11. Hickey, M.J., Malone, C.C., Erickson, K.E., Gomez, G.G., Young, E.L., Liau, L.M., Prins, R.M., Kruse, C.A. (2012) Implementing preclinical study findings to protocol design: translational studies with alloreactive CTL for gliomas, Am J. Transl. Res., 4:114-126.
12. 12. Ma, W., Chen, M., McElroy M., Zhang, Y., Ozkan, C., Bouvet, M., Kruse, C.A., Grotjahn, D., Ichim, T., Minev, B. (2012) PLGA nanoparticle-mediated delivery of tumor antigenic peptides elicits effective immune responses. Intl. J. Nanomed. 7, 1475-1487.
13. 13. Haga, K., Lin, A., Hickey, M.J., Gomez, G.G., Logg, C.R., Kimura, T., Hiraoka, K., Matsumoto, H., Ohno, I., Kruse, C.A., Kasahara, N. (2012) Combined Cellular Therapy with Alloreactive Cytotoxic T Lymphocytes and Prodrug Activator Gene Therapy with Replicating Retrovirus Vectors in a Brain Tumor Model, Mol. Therapy, submitted.
    

Read my PubMed publications