2005-2006 Grant

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<bR> <bR> </tD> </tR> </TABLE></div> <div> <I><B> <TABLE BORDER="0" CELLPADDING="2" CELLSPACING="1" WIDTH="626" BORDERCOLORLIGHT="#C0C0C0" BORDERCOLORDARK="#808080" FRAME="BOX" RULES="ALL" HSPACE="0" VSPACE="0" > <tR> <tD VALIGN=TOP HEIGHT= 3396 WIDTH="620"><div> <FONT SIZE="5" COLOR="#000066" FACE="Arial" ><B>Billy Grey </B> </FONT><A HREF="2011grant.htm" TARGET="_top" TITLE="2011 Grant "><U><2011</U></A> <<A HREF="2010grant.htm" TARGET="_top" TITLE="2010 Grant "><U>2010 </U></A><<A HREF="2009grant.htm" TARGET="_top" TITLE="2009 Grant "><U>2009</U></A> <<A HREF="id43.htm" TARGET="_top" TITLE="2008 Grant "><U>2008</U></A> < <A HREF="id39.htm" TARGET="_top" TITLE="2007 Grant "><U>2007</U></A> <B>< </B><A HREF="id36.htm" TARGET="_top" TITLE="20052006 Grant "><U><B>2005-2006</B></U></A> < <A HREF="id32.htm" TARGET="_top" TITLE="2004 Grant "><U>2003-2004</U></A> < <A HREF="id30.htm" TARGET="_top" TITLE="2002 Grant"><U>2002</U></A></div> <bR> <div> <B>Chair of Research: 2005-2006</B></div> <div> 2005-2006: 2nd Year of $200,000 Grant Award<FONT SIZE="5" COLOR="#000066" FACE="Arial" ><B> </B></FONT></div> <div> <B>Duane A. Mitchell, MD, Ph.D.</B></div> <div> <B>Duke University Medical Center, Durham, North Carolina</B></div> <div> Identification and Immunologic Targeting of CMV Antigens Expressed in Malignant Gliomas</div> <bR> <bR> <DIV ALIGN="LEFT"></DIV> <div> <TABLE BORDER="0" CELLPADDING="2" CELLSPACING="0" WIDTH="552" BORDERCOLORLIGHT="#000099" BORDERCOLORDARK="#0000CC" FRAME="BOX" RULES="ALL" HSPACE="0" VSPACE="0" BGCOLOR=#000033 > <tR> <tD VALIGN=TOP HEIGHT= 435 WIDTH="548"><div> <I><B>Identification and Immunologic Targeting of CMV Antigens </B></I></div> <div> <I><B>Expressed in Malignant Gliomas</B></I></div> <div> Ken Grey & Dr. Duane Mitchell<IMG SRC="07af4770.jpg" border=0 width="500" height="375" ALIGN="BOTTOM" HSPACE="0" VSPACE="0"></div> </tD> </tR> </TABLE></div> <div> The prognosis for patients diagnosed with malignant gliomas remains very poor and the non-specific nature of standard treatment often results in damage to surrounding normal brain.  Immunotherapy directed against tumor-specific antigens holds the potential to target malignant cells more precisely, but it is severely limited because we do not have a strong understanding of the tumor rejection antigens present in human cancers.  The recent finding that human cytomegalovirus (HCMV) propagates in a large number of malignant gliomas, without infecting surrounding normal brain cells, promises to direct brain tumor immunotherapy against immunogenic viral targets.</div> <bR> <DIV ALIGN="LEFT"></DIV> <div> Recent clinical trials highlight the benefit of adoptive immunotherapy, in setting of chemotherapy-induced lymphopenia, as a powerful way to guide the recovering immune system toward anti-tumor recognition.  We propose to investigate CMV antigen expression in malignant glioma specimens, and evaluate adoptive immunotherapy following treatment-induced lymphopenia using murine model of CMV-associated astrocytomas.</div> <bR> <div> <B><U>UPDATES: BILLY GREY RESEARCH GRANT 2005-2006</U></B></div> <bR> <bR> <bR> <div> April 13, 2009</div> <bR> <div> Ken Grey, Vice Chair, NBTS </div> <div> President </div> <div> Marshall & Sterling Upstate, Inc. </div> <div> 300 Route 23B, Leeds, N.Y. 12451 </div> <div> Tel (518) 943-3900 ext. 17 </div> <div> Fax (518) 943-7440 </div> <div> Cell (518) 573-5481 </div> <bR> <bR> <div> Dear Ken,</div> <bR> <div>      Great to hear from you and truly glad to hear about the significant impact Team Billy is making on the support and advancement of brain tumor research.  I can tell you personally that the contributions your organization and the National Brain Tumor Society have made to our work here at the placePlaceNamePreston PlaceNameRobert PlaceNameTisch PlaceNameBrain PlaceNameTumor PlaceTypeCenter at Duke have definitely been instrumental and are already paying dividends in the advancement of new therapies for patients with malignant brain tumors.</div> <bR> <div>      As you are aware, the work supported by the National Brain Tumor Society through the Billy Grey Chair of Research award I received has been a key source of funding leading to our publishing the first confirmatory report of the association between human Cytomegalovirus (CMV) and malignant gliomas since Dr. Charles Cobbs original findings published in 2002.  This work, and the development of immunotherapy targeting CMV in brain tumors, has received national media attention, with press coverage in Newsweek, Scientific American, The Economist, and NBC World News.  This past year has been extraordinary for increasing public awareness of about malignant brain tumors and the funding your organization provides is often the critically needed “start-up” money that will lead to the breakthroughs of tomorrow in this field.  We are continuing to pursue CMV-directed immunotherapy for patients with glioblastoma and are in the process of formulating our vaccine into an “off-the-shelf” version that may be more widely available to patients at other centers if this new version shows clinical promise.   We hope to initial clinical trials with this newer version of cancer vaccine in the very near future.   </div> <bR> <div>      The funds you raise are critically important to allow investigators to take some risks and venture into new areas of research that may hold promise for better understanding and treatment of brain cancers.  We know the knowledge we have today is not yet enough to cure malignant brain tumors in the majority of patients, but thanks to the undying spirit and continual efforts of organizations like the National Brain Tumor Society and Team Billy, we are continually getting closer to the day when we can tell patients and families of persons affected by a malignant brain tumor that we have the answers and the tools to definitely beat this horrible disease.  </div> <bR> <bR> <div> With sincerest respect and gratitude for all that you do,</div> <bR> <DIV ALIGN="LEFT"></DIV> <div> <IMG SRC="21208530.jpg" border=0 width="264" height="83" ALIGN="BOTTOM" HSPACE="0" VSPACE="0"></div> <div> <B>Duane A. Mitchell, M.D., Ph.D.</B></div> <bR> <DIV ALIGN="LEFT"></DIV> <div> Alex H. Sands, Jr. Research Building, Room 213  <FONT SIZE="1" COLOR="#003366" FACE="Symbol" >·</FONT>  Box 3050 <FONT SIZE="1" COLOR="#003366" FACE="Symbol" >·</FONT> Durham, NC <FONT SIZE="1" COLOR="#003366" FACE="Symbol" >·</FONT> 27710  </div> <div> tel (919) 684-1951 <FONT SIZE="1" COLOR="#003366" FACE="Symbol" >·</FONT> fax: (919) 684-9045 <FONT SIZE="1" COLOR="#003366" FACE="Symbol" >· </FONT> d.mitchell@duke.edu</div> <div> <B>Research that was directly funded from  the </B><I><B>Billy Grey Research Chair (BTS),</B></I></div> <div> <I><B>Accelerate Brain Cancer Cure Foundation, and the NIH SPORE in Brain Cancer at Duke University Medical Center</B></I><B> received Institutional Review Board and FDA approval for a clinical trial targeting CMV in malignant gliomas. </B><I>See letter below from Dr. Duane Mitchell:</I></div> <bR> <DIV ALIGN="LEFT"></DIV> <div> <B>DUKE UNIVERSITY MEDICAL CENTER</B></div> <div> <B>Duane A. Mitchell, M.D., Ph.D.</B></div> <div> <B>Assistant Research Professor of Neurosurgery</B></div> <div> <B>The Preston Robert Tisch Brain Tumor Center at Duke</B></div> <div> <B>Department of Surgery</B></div> <div> <B>Division of Neurosurgery</B></div> <DIV ALIGN="LEFT"></DIV> <div> February 10, 2006</div> <div> Dear Ken Grey,</div> <div>             I wanted to update you on the progress we have made in the research that you, your family, and The Brain Tumor Society have generously supported.  We just received Institutional Review Board and Food and Drug Administration approval for a clinical trial targeting human cytomegalovirus antigens expressed in malignant glioma.  This trial will use dendritic cell vaccination combined with transfer of lymphocytes after the administration of temozolomide in attempt to combine the killing capacity of chemotherapy with potent immunotherapy.  Dr. John H. Sampson and I are Co-Principal Investigators on this trial, and we have already begun enrollment of our first patients to receive this new therapy.</div> <bR> <div> <B>           </B>The funding for the Billy Grey Chair of Research has been invaluable in assisting the translation of this work from preclinical investigation to implementation in a clinical trial, and we are very optimistic about the benefits that this trial will bring to the immunologic treatment of malignant brain tumors.  A major focus of the research I have been conducting with the support of the Chair has been on determining how immunotherapy can best be conducted in conjunction with temozolomide treatment, which is now a mainstay in the treatment of high-grade gliomas. We have very promising data that immunologic responses can actually be enhanced by the appropriate timing of temozolomide therapy and cellular immunotherapy and this clinical trial will address this possibility in patients receiving vaccines and lymphocyte infusions in between cycles of temozolomide.</div> <div>     </div> <div>        I cannot emphasize enough how important the support that private foundations such as The Brain Tumor Society (BTS) and Accelerate Brain Cancer Cure Foundation (ABCC) have been in support of this work.  In the face of constrained federal budgets, private foundation and donor support is becoming increasingly critical to the advancement of brain tumor research.  The support from the Billy Grey Chair of Research and ABCC were instrumental in our laboratory receiving NIH funding to support this trial.</div> <div>    </div> <div>         I look forward to keeping you updated on our progress, and we will keep working hard on our end to ensure that your efforts to increase awareness and raise funds for brain tumor research are being leveraged as resourcefully as possible here at Duke.</div> <div>        </div> <div>     Thank you again for all that you and those who support The Billy Grey Chair of Research do in the fight against this disease.                                   Sincerely,</div> <bR> <div>                                                             <IMG SRC="08d56650.png" border=0 width="342" height="101" ALIGN="BOTTOM" HSPACE="0" VSPACE="0"></div> <DIV ALIGN="LEFT"></DIV> <div> <B>Box 3050 • Durham, NC • 27710 • tel (919) 684-1951• fax: (919) 684-9045</B></div> <div> <B>d.mitchell@duke.edu</B></div> <bR> <div> <B><U>UPDATE: RESEARCH REVIEW!</U></B></div> <bR> <div> <I><B>Identification and Immunologic Targeting of CMV Antigens </B></I></div> <div> <I><B>Expressed in Malignant Gliomas</B></I></div> <bR> <div> <B>Grant Recipient</B></div> <div> Duane A. Mitchell, MD, Ph.D.</div> <div> Duke University Medical Center, Durham, North Carolina</div> <bR> <div> "I think that Duane’s progress is impressive. He has generated significant data to support an association between CMV infection and gliomas. Based on brain tumor models in mice, he undertook a pilot clinical trial of combination in patients pf temazolomide, dendritic cell vaccination, and adoptive cellular therapy. The results of this early stage study appear quite promising, with evidence of tumor regression and a favorable time to progression. These findings will now form the basis of a second trial which will employ a further refinement of the method of generating T cells for adoptive therapy. Duane’s ability to translate principles from the murine models to glioma patients is unusual; there are few investigators who have demonstrated this capacity. I think that the BTS made a wise investment."</div> <bR> <DIV ALIGN="LEFT"></DIV> <div> <I><B>-Grant Reviewer</B></I></div> <div> <I><B>June 2007</B></I></div> </tD> </tR> </TABLE></B></I></div> <bR> <bR> </td> </tr></table></body>