Mathematical modeling of cellular immunotherapy for high grade gliomas

00:00 14-01-2009
<p class="MsoNormal" dir="ltr" style="DIRECTION: ltr; unicode-bidi: embed; TEXT-ALIGN: left"><font face="Arial" size="2"><span style="FONT-SIZE: 14px; FONT-FAMILY: Arial">Dear Colleagues,</span></font></p> <p class="MsoNormal" dir="ltr" style="DIRECTION: ltr; unicode-bidi: embed; TEXT-ALIGN: left"><font face="Arial" size="2"><span style="FONT-SIZE: 14px; FONT-FAMILY: Arial"> </span></font><font face="Arial" size="2"><span style="FONT-SIZE: 14px; FONT-FAMILY: Arial">Our next Mathematical Colloquium will take place on <a title="http://www.multitran.ru/c/m.exe?t=2729_1_2" href="http://www.multitran.ru/c/m.exe?t=2729_1_2"><font title="http://www.multitran.ru/c/m.exe?t=2729_1_2" color="black"><span title="http://www.multitran.ru/c/m.exe?t=2729_1_2" style="COLOR: windowtext; TEXT-DECORATION: none">Wednesday</span></font></a>, January 14, at 15:00.</span></font></p> <p class="MsoNormal" dir="ltr" style="DIRECTION: ltr; unicode-bidi: embed; TEXT-ALIGN: left"><font face="Arial" size="2"><span style="FONT-SIZE: 14px; FONT-FAMILY: Arial"> </span></font><font face="Arial" size="2"><span style="FONT-SIZE: 14px; FONT-FAMILY: Arial">       Speaker: Dr. Natalie Kronik</span></font></p> <p class="MsoNormal" dir="ltr" style="DIRECTION: ltr; unicode-bidi: embed; TEXT-ALIGN: left"><font face="Arial" size="2"><span style="FONT-SIZE: 14px; FONT-FAMILY: Arial">        Affiliation:  Institute for Medical BioMathematics, <st1:place w:st="on"><st1:city w:st="on">Bene-Ataroth</st1:city> <st1:postalcode w:st="on">60991</st1:postalcode>, <st1:country-region w:st="on">Israel</st1:country-region></st1:place></span></font></p> <p class="MsoNormal" dir="ltr" style="DIRECTION: ltr; unicode-bidi: embed; TEXT-ALIGN: left"><font face="Arial" size="2"><span style="FONT-SIZE: 14px; FONT-FAMILY: Arial">        Title:     Mathematical modeling of cellular immunotherapy for high grade gliomas</span></font></p> <p class="MsoNormal" dir="ltr" style="DIRECTION: ltr; unicode-bidi: embed; TEXT-ALIGN: left"><font face="Arial" size="2"><span style="FONT-SIZE: 14px; FONT-FAMILY: Arial">        Date: January 14, 2009</span></font></p> <p class="MsoNormal" dir="ltr" style="DIRECTION: ltr; unicode-bidi: embed; TEXT-ALIGN: left"><font face="Arial" size="2"><span style="FONT-SIZE: 14px; FONT-FAMILY: Arial">        Time: 15:00 </span></font></p> <p class="MsoNormal" dir="ltr" style="DIRECTION: ltr; unicode-bidi: embed; TEXT-ALIGN: left"><font face="Arial" size="2"><span style="FONT-SIZE: 14px; FONT-FAMILY: Arial">        Venue: <font color="navy"><span style="COLOR: navy"> </span></font><b><span style="FONT-WEIGHT: bold">Room 426/8, <st1:place w:st="on"><st1:placename w:st="on">Science</st1:placename> <st1:placetype w:st="on">Building</st1:placetype></st1:place></span></b></span></font></p> <p class="MsoNormal" dir="ltr" style="DIRECTION: ltr; unicode-bidi: embed; TEXT-ALIGN: left"><font face="Arial" size="2"><span style="FONT-SIZE: 14px; FONT-FAMILY: Arial">      </span></font><font face="Arial" size="2"><span style="FONT-SIZE: 14px; LINE-HEIGHT: 150%; FONT-FAMILY: Arial">Abstract:  High grade gliomas (HGG) are highly aggressive pathological primary adult and pediatric brain tumors with a median life expectancy of 18-60 months, depending on tumor grade. So far, no treatment strategy has been efficacious in the treatment of HGGs, including state-of-the-art combinations of surgery, chemotherapy and radiation. Recently, adoptive T-cell therapy (aTCT), by ex vivo expansion of modified T lymphocytes, has been suggested for HGG treatment. However, to date this strategy has met only anecdotal success. To explain why success of this promising method is elusive we have constructed a detailed mathematical model. Our model factors in tumor cell biology, adoptively transferred T-cells, key cytokines, and major histocompatibility receptors, which govern the tumor microenvironment. </span></font></p> <p class="MsoNormal" dir="ltr" style="DIRECTION: ltr; TEXT-INDENT: 22.5pt; LINE-HEIGHT: 150%; TEXT-AUTOSPACE: ideograph-numeric; unicode-bidi: embed; TEXT-ALIGN: left"><font face="Arial" size="2"><span style="FONT-SIZE: 14px; LINE-HEIGHT: 150%; FONT-FAMILY: Arial">Through mathematical analysis, we show that the treatment outcome relies heavily on patient-specific disease parameters, such as tumor doubling time and disease grade. Computer simulations based on the mathematical model have successfully retrieved the results of a clinical trial by Kruse et al. (1997) and suggested that the aTCT regimen used for the highest grade tumor was 20 fold lower than the therapeutic level. Such considerations as disease grade are currently not taken into account when planning aTCT. Our mathematical results strongly suggest that under the currently available T-cell therapy methodologies, individual planning of dosing schedules may contribute to improving the success of aTCT immunotherapy for HGG as well as for other malignancies. </span></font></p> <p class="MsoNormal" dir="ltr" style="DIRECTION: ltr; unicode-bidi: embed; TEXT-ALIGN: left"><font face="Arial" size="2"><span style="FONT-SIZE: 14px; FONT-FAMILY: Arial"> </span></font><font face="Arial" size="2"><span style="FONT-SIZE: 14px; FONT-FAMILY: Arial">Light refreshments will be served at 14:45 am. Everybody is welcome.</span></font></p> <p class="MsoNormal" dir="ltr" style="DIRECTION: ltr; unicode-bidi: embed; TEXT-ALIGN: left"><font face="Arial" size="2"><span style="FONT-SIZE: 14px; FONT-FAMILY: Arial"> </span></font><font face="Arial" size="2"><span style="FONT-SIZE: 14px; FONT-FAMILY: Arial">Holon Institute of Technology, <st1:address w:st="on"><st1:street w:st="on">52 Golomb St</st1:street>, <st1:city w:st="on">Holon</st1:city></st1:address>, 03-5026560</span></font></p> <p class="MsoNormal" dir="ltr" style="DIRECTION: ltr; unicode-bidi: embed; TEXT-ALIGN: left"><font face="Arial" size="2"><span style="FONT-SIZE: 14px; FONT-FAMILY: Arial"></span></font> </p>