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<p class="MsoNormal" align="center" style="text-align:center"><a name="_Hlk176356590"><img width="334" height="40" style="width:3.4791in;height:.4166in" id="Picture_x0020_12" src="cid:image001.jpg@01DAFF82.28DA2FB0"><o:p></o:p></a></p>
<p class="MsoNormal" style="margin-bottom:6.0pt"><span style="mso-bookmark:_Hlk176356590"><span style="font-size:8.0pt;color:#7F7F7F;mso-fareast-language:SL"><o:p> </o:p></span></span></p>
<p class="MsoNormal" style="margin-bottom:6.0pt"><span style="mso-bookmark:_Hlk176356590"><span style="font-size:8.0pt;color:#7F7F7F;mso-fareast-language:SL"><o:p> </o:p></span></span></p>
<p class="MsoNormal" style="margin-bottom:6.0pt"><span style="mso-bookmark:_Hlk176356590"><span style="font-size:8.0pt;color:#7F7F7F;mso-fareast-language:SL"><o:p> </o:p></span></span></p>
<p class="MsoNormal" align="center" style="text-align:center"><span style="mso-bookmark:_Hlk176356590"><span style="font-size:14.0pt;color:#7F7F7F">Nacionalni inštitut za biologijo Vas vabi,
<o:p></o:p></span></span></p>
<p class="MsoNormal" align="center" style="text-align:center"><span style="mso-bookmark:_Hlk176356590"><span style="font-size:14.0pt;color:#7F7F7F">da se udeležite seminarja<o:p></o:p></span></span></p>
<p class="MsoNormal" align="center" style="text-align:center"><span style="mso-bookmark:_Hlk176356590"><span style="font-size:14.0pt;color:#7F7F7F"><o:p> </o:p></span></span></p>
<p class="MsoNormal" align="center" style="text-align:center"><span style="mso-bookmark:_Hlk176356590"><b><span lang="EN-US" style="font-size:18.0pt;color:#2A8C46;letter-spacing:.05pt">»</span></b></span><span style="mso-bookmark:_Hlk176356590"><b><span style="font-size:20.0pt;color:#2A8C46;letter-spacing:.05pt">Expanding
the therapeutic index of adoptive T cell therapy for solid cancer</span></b></span><span style="mso-bookmark:_Hlk176356590"><b><span lang="EN-US" style="font-size:18.0pt;color:#2A8C46;letter-spacing:.05pt">«,
<o:p></o:p></span></b></span></p>
<p class="MsoNormal" align="center" style="text-align:center"><span style="mso-bookmark:_Hlk176356590"><b><span lang="EN-US" style="font-size:9.0pt;color:#2A8C46;letter-spacing:.05pt"><o:p> </o:p></span></b></span></p>
<p class="MsoNormal" align="center" style="text-align:center"><span style="mso-bookmark:_Hlk176356590"><span lang="EN-US" style="font-size:14.0pt;color:#7F7F7F;letter-spacing:.05pt">ki ga bo predstavil<o:p></o:p></span></span></p>
<p class="MsoNormal" align="center" style="text-align:center"><span style="mso-bookmark:_Hlk176356590"><span lang="EN-US" style="font-size:6.0pt;color:#7F7F7F;letter-spacing:.05pt"><o:p> </o:p></span></span></p>
<p class="MsoNormal" align="center" style="text-align:center"><span style="mso-bookmark:_Hlk176356590"><b><span lang="EN-US" style="font-size:28.0pt;color:#005E9C;letter-spacing:.05pt">Daniel J. Powell Jr., Ph.D.<o:p></o:p></span></b></span></p>
<p class="MsoNormal" align="center" style="text-align:center"><span style="mso-bookmark:_Hlk176356590"><span lang="EN-US" style="font-size:12.0pt;color:#7F7F7F;letter-spacing:.05pt">Professor of Pathology and Laboratory Medicine<o:p></o:p></span></span></p>
<p class="MsoNormal" align="center" style="text-align:center"><span style="mso-bookmark:_Hlk176356590"><span lang="EN-US" style="font-size:12.0pt;color:#7F7F7F;letter-spacing:.05pt">On site Director, PENN Tumor BioTrust<o:p></o:p></span></span></p>
<p class="MsoNormal" align="center" style="text-align:center"><span style="mso-bookmark:_Hlk176356590"><span lang="EN-US" style="font-size:12.0pt;color:#7F7F7F;letter-spacing:.05pt">Director of Education, Parker Institute for Cancer Immunotherapy<o:p></o:p></span></span></p>
<p class="MsoNormal" align="center" style="text-align:center"><span style="mso-bookmark:_Hlk176356590"><span lang="EN-US" style="font-size:12.0pt;color:#7F7F7F;letter-spacing:.05pt">Scientific Director of Immunotherapy, Division of Gynecologic Oncology<o:p></o:p></span></span></p>
<p class="MsoNormal" align="center" style="text-align:center"><span style="mso-bookmark:_Hlk176356590"><span lang="EN-US" style="font-size:12.0pt;color:#7F7F7F;letter-spacing:.05pt">Perelman School of Medicine at the University of Pennsylvania<o:p></o:p></span></span></p>
<p class="MsoNormal" align="center" style="text-align:center"><span style="mso-bookmark:_Hlk176356590"><span lang="EN-US" style="font-size:12.0pt;color:#7F7F7F;letter-spacing:.05pt"><o:p> </o:p></span></span></p>
<p class="Default" align="center" style="margin-bottom:6.0pt;mso-para-margin-bottom:.5gd;text-align:center">
<span style="mso-bookmark:_Hlk176356590"><span style="font-size:2.0pt;font-family:"Arial",sans-serif;color:#7F7F7F"><o:p> </o:p></span></span></p>
<p class="Default" style="margin-bottom:6.0pt;mso-para-margin-bottom:.5gd;text-indent:148.85pt">
<span style="mso-bookmark:_Hlk176356590"><span style="font-size:1.0pt;font-family:"Arial",sans-serif;color:#7F7F7F"><o:p> </o:p></span></span></p>
<p class="Default" align="center" style="text-align:center"><span style="mso-bookmark:_Hlk176356590"><img width="197" height="196" style="width:2.052in;height:2.0416in" id="Picture_x0020_11" src="cid:image002.jpg@01DAFF82.28DA2FB0" alt="A person in a suit
Description automatically generated"></span><span style="mso-bookmark:_Hlk176356590"><b><span style="font-size:16.0pt;font-family:"Aptos",sans-serif;color:#105A97"><o:p></o:p></span></b></span></p>
<p class="MsoNoSpacing"><span style="mso-bookmark:_Hlk176356590"><span style="font-size:1.0pt"><o:p> </o:p></span></span></p>
<p class="MsoNoSpacing"><span style="mso-bookmark:_Hlk176356590"><span style="font-size:8.0pt"><o:p> </o:p></span></span></p>
<p class="MsoNormal" align="center" style="text-align:center"><span style="mso-bookmark:_Hlk176356590"><b><span style="font-size:14.0pt;color:#2A8C46;letter-spacing:.05pt">Seminar bo v torek, 24. septembra 2024, ob 11. uri<o:p></o:p></span></b></span></p>
<p class="MsoNormal" align="center" style="text-align:center"><span style="mso-bookmark:_Hlk176356590"><b><span style="font-size:14.0pt;color:#2A8C46;letter-spacing:.05pt">na Nacionalnem inštitutu za biologijo,</span></b></span><span style="mso-bookmark:_Hlk176356590"><span style="font-size:14.0pt;color:#2A8C46;letter-spacing:.05pt">
<o:p></o:p></span></span></p>
<p class="MsoNormal" align="center" style="text-align:center"><span style="mso-bookmark:_Hlk176356590"><span style="font-size:12.0pt;color:#7F7F7F;letter-spacing:.05pt">Večna pot 121, 1000 Ljubljana, v veliki predavalnici
<o:p></o:p></span></span></p>
<p class="MsoNormal" align="center" style="text-align:center"><span style="mso-bookmark:_Hlk176356590"><span style="font-size:12.0pt;color:#7F7F7F;letter-spacing:.05pt">(v prvem nadstropju, glavni vhod C/D).</span></span><span style="mso-bookmark:_Hlk176356590"><span style="font-size:12.0pt;color:#2A8C46;letter-spacing:.05pt"><o:p></o:p></span></span></p>
<p class="MsoNormal" align="center" style="text-align:center"><span style="mso-bookmark:_Hlk176356590"><span style="font-size:4.0pt"><o:p> </o:p></span></span></p>
<p class="MsoNormal" style="text-align:justify"><span style="mso-bookmark:_Hlk176356590"><b><u><span style="font-size:12.0pt;color:#636363"><o:p><span style="text-decoration:none"> </span></o:p></span></u></b></span></p>
<p class="MsoNormal" align="center" style="text-align:center"><span style="mso-bookmark:_Hlk176356590"><b><u><span lang="EN-US" style="font-size:10.0pt;color:#005E9C">Abstract:</span></u></b></span><span style="mso-bookmark:_Hlk176356590"><u><span lang="EN-US" style="font-size:10.0pt;color:#636363"><o:p></o:p></span></u></span></p>
<p class="MsoNormal" style="text-align:justify"><span style="mso-bookmark:_Hlk176356590"><span lang="EN-US" style="font-size:10.0pt;color:#636363">The advent of CAR T cell therapy has revolutionized treatment of certain types of hematologic malignancies, yet
achieving similar efficacy against solid tumors in the absence of significant toxicities remains a challenge. Our recent clinical trial results indicate that infused CAR T cells can infiltrate solid tumors and mediate modest tumor regression, yet creating
curative therapy will first necessitate a better understanding of the limits of therapy and the mechanisms of resistance. To begin to address this issue, our research efforts have focused on maximizing the tumor antigen targeting capabilities of T cell products;
identifying and overcoming mechanisms of immune suppression and resistance; and recruiting endogenous cells to participate in, and extend the breadth of, the immune response to cancer. Deep phenotypic and transcriptional analysis of naturally occurring, tumor
infiltrating T cells (TILs) is now illuminating the requirements of effective T cell immunotherapy, serving as a guidepost for improving T cell product potency. With this understanding, tumor-reactive TILs can now be enriched directly from tumors for clinical
application and synthetic biology can be applied to instill endogenous antitumor T cells with supraphysiological properties that bolster functional activity. Still, once administered to patients, CAR T cells and TILs need to contend with the hostile and immunosuppressive
tumor microenvironment. As such, our ongoing efforts are focused on disentangling the suppressive cellular and acellular constituents of the microenvironment to better understand the major contributors to immune suppression in solid tumors. While myeloid cells
in tumors have the potential to have pro-inflammatory activity and deliver positive costimulatory signals to T cells, myeloid cells are easily corrupted and repolarized to a suppressive phenotype by the tumor microenvironment yet durable deletion or reprogramming
of these cells remains a challenge. Our recent work has identified a biomarker of suppressive myeloid cells in tumors in mice, which can be targeted by CAR T cells, and this work is now being extended to human tumor studies. Further, we find that the acellular
milieu of tumors and their surrounding fluid has properties that can either improve or limit CAR T cell activity, which may be capitalized upon to create a more favorable microenvironment into which CAR T cells can be administered. Addressing such gaps in
knowledge is central to the development of clinically actionable, synthetic biology approaches that overcome these immunologic hurdles, mitigate toxicity and bolster the effectiveness of adoptive T cell therapy against solid tumors.<o:p></o:p></span></span></p>
<p class="MsoNormal" style="text-align:justify"><span style="mso-bookmark:_Hlk176356590"><span lang="EN-US" style="font-size:10.0pt;color:#636363"><o:p> </o:p></span></span></p>
<p class="MsoNormal" style="text-align:justify"><span style="mso-bookmark:_Hlk176356590"><span style="font-size:10.0pt;color:#636363"><o:p> </o:p></span></span></p>
<p align="center" style="mso-margin-top-alt:0cm;margin-right:3.25pt;margin-bottom:0cm;margin-left:14.2pt;text-align:center">
<span style="mso-bookmark:_Hlk176356590"><strong><span style="font-size:11.0pt;font-family:"Arial",sans-serif">Vljudno vabljeni! Seminar bo potekal v angleškem jeziku.</span></strong></span><span style="mso-bookmark:_Hlk176356590"><strong><span style="font-size:11.0pt;font-family:"Arial",sans-serif;font-weight:normal"><o:p></o:p></span></strong></span></p>
<p align="center" style="mso-margin-top-alt:0cm;margin-right:3.25pt;margin-bottom:0cm;margin-left:14.2pt;text-align:center">
<span style="mso-bookmark:_Hlk176356590"><strong><span style="font-size:11.0pt;font-family:"Arial",sans-serif"><o:p> </o:p></span></strong></span></p>
<p align="center" style="mso-margin-top-alt:0cm;margin-right:3.25pt;margin-bottom:0cm;margin-left:14.2pt;text-align:center">
<span style="mso-bookmark:_Hlk176356590"><strong><span style="font-size:11.0pt;font-family:"Arial",sans-serif">Na seminar se je potrebno prijaviti.
</span></strong></span><span style="mso-bookmark:_Hlk176356590"><strong><span style="font-size:11.0pt;font-family:"Arial",sans-serif;color:#00994E">Registracijski obrazec je</span></strong></span><span style="mso-bookmark:_Hlk176356590"><strong><span style="font-size:11.0pt;font-family:"Arial",sans-serif">
</span></strong></span><a href="https://docs.google.com/forms/d/e/1FAIpQLSeBd67gSazE8OC22o6zOONIyWLMzkfKS6Tkrq3EeN5-Vzhucw/viewform"><span style="mso-bookmark:_Hlk176356590"><span style="font-size:11.0pt">tukaj</span></span><span style="mso-bookmark:_Hlk176356590"></span></a><span style="mso-bookmark:_Hlk176356590"><strong><span style="font-size:11.0pt;font-family:"Arial",sans-serif">.
<o:p></o:p></span></strong></span></p>
<p class="MsoNormal" align="center" style="margin-bottom:6.0pt;text-align:center">
<span style="mso-bookmark:_Hlk176356590"><span style="color:#636363"><o:p> </o:p></span></span></p>
<p class="MsoNormal" align="center" style="text-align:center"><span style="mso-bookmark:_Hlk176356590"><span style="color:#636363;mso-ligatures:none">Dodatne informacije: dr. Anže Smole,
</span></span><span style="mso-bookmark:_Hlk176356590"></span><a href="mailto:anze.smole@nib.si"><span style="mso-bookmark:_Hlk176356590"><span style="mso-ligatures:none">anze.smole@nib.si</span></span><span style="mso-bookmark:_Hlk176356590"></span></a><o:p></o:p></p>
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