Clinical Cell Processing and Purification

The Focus Group Clinical Cell Processing and Purification is dedicated to the development of clinical cell-therapeutics for the treatment of infections as well as certain forms of cancer or other immunologically related diseases. Especially the identification, targeting and isolation of defined cells for adoptive cell therapies are core interests of the group.

The focus group consisted of Prof. Stanley Riddell (Hans Fischer Senior Fellow), Dr. Christian Stemberger (Carl von Linde Junior Fellow) and Prof. Dirk Busch (Host), who combined their interests with the goal to to set up a most advanced platform supporting cell therapy applications.

Key interests encompass the identification and evaluation of appropriate target cells such as different types of T cells, NK cells or (hematopoietic/mesenchymal) stem cells as well as uncovering specific advantages of primary (minimally manipulated) cells for cell therapy. Furthermore, identification of appropriate target (T cell) antigens on infected and malignant cells, as well as a better understanding of mechanisms guiding/regulating cell differentiation and in vivo survival will become crucial aspects examined in within the focus group.

Molecular methods are being developed that allow for highly specific and reversible targeting of desired cell populations. Together with the development of technically advanced selection and processing techniques (like magnetic cell sorting and flow cytometry, cryo-preservation) GMP-grade cellular products will be generated. The integration of such a compact workflow comprising the identification, selection, isolation and preservation of highly functional and minimally manipulated cell populations should facilitate the broader integration of cell therapies into individualized medical care.

TUM-IAS funded doctoral candidates:
Jeanette Bet, Medical Microbiology, Immunology and Hygiene
Paulina Paszkiewicz (PhD in 2014)

Postdoc:
Stefan Dreher, Medical Microbiology, Immunology and Hygiene

Publications by the Focus Group

2016

  • Buchholz, Veit R.; Schumacher, Ton N.M.; Busch, Dirk H.: T Cell Fate at the Single-Cell Level. Annual Review of Immunology 34 (1), 2016, 65-92 more…
  • Busch, Dirk H.; Fräßle, Simon P.; Sommermeyer, Daniel; Buchholz, Veit R.; Riddell, Stanley R.: Role of memory T cell subsets for adoptive immunotherapy. Seminars in Immunology 28 (1), 2016, 28-34 more…
  • Liu, Lingfeng; Sommermeyer, Daniel; Cabanov, Alexandra; Kosasih, Paula; Hill, Tyler; Riddell, Stanley R: Inclusion of Strep-tag II in design of antigen receptors for T-cell immunotherapy. Nature Biotechnology 34 (4), 2016, 430-434 more…
  • Liu, Lingfeng; Sommermeyer, Daniel; Cabanov, Alexandra; Kosasih, Paula; Hill, Tyler; Riddell, Stanley R: Inclusion of Strep-tag II in design of antigen receptors for T-cell immunotherapy. Nature Biotechnology 34 (4), 2016, 430-434 more…
  • Nauerth, Magdalena; Stemberger, Christian; Mohr, Fabian; Weißbrich, Bianca; Schiemann, Matthias; Germeroth, Lothar; Busch, Dirk H.: Flow cytometry-based TCR-ligandKoff-rate assay for fast avidity screening of even very small antigen-specific T cell populations ex vivo. Cytometry Part A 89 (9), 2016, 816-825 more…
  • Paszkiewicz, Paulina J.; Fräßle, Simon P.; Srivastava, Shivani; Sommermeyer, Daniel; Hudecek, Michael; Drexler, Ingo; Sadelain, Michel; Liu, Lingfeng; Jensen, Michael C.; Riddell, Stanley R.; Busch, Dirk H.: Targeted antibody-mediated depletion of murine CD19 CAR T cells permanently reverses B cell aplasia. Journal of Clinical Investigation 126 (11), 2016, 4262-4272 more…
  • Schober, Kilian; Busch, Dirk H: A synergistic combination: using RNAseq to decipher both T-cell receptor sequence and transcriptional profile of individual T cells. Immunology and Cell Biology 94 (6), 2016, 529-530 more…
  • Schober, Kilian; Busch, Dirk H.: TIL 2.0: More effective and predictive T-cell products by enrichment for defined antigen specificities. European Journal of Immunology 46 (6), 2016, 1335-1339 more…
  • Turtle, Cameron J.; Hanafi, Laïla-Aïcha; Berger, Carolina; Gooley, Theodore A.; Cherian, Sindhu; Hudecek, Michael; Sommermeyer, Daniel; Melville, Katherine; Pender, Barbara; Budiarto, Tanya M.; Robinson, Emily; Steevens, Natalia N.; Chaney, Colette; Soma, Lorinda; Chen, Xueyan; Yeung, Cecilia; Wood, Brent; Li, Daniel; Cao, Jianhong; Heimfeld, Shelly; Jensen, Michael C.; Riddell, Stanley R.; Maloney, David G.: CD19 CAR–T cells of defined CD4+:CD8+ composition in adult B cell ALL patients. Journal of Clinical Investigation 126 (6), 2016, 2123-2138 more…

2015

  • Dargel, Christina; Bassani-Sternberg, Michal; Hasreiter, Julia; Zani, Fabio; Bockmann, Jan-Hendrik; Thiele, Frank; Bohne, Felix; Wisskirchen, Karin; Wilde, Susanne; Sprinzl, Martin F.; Schendel, Dolores J.; Krackhardt, Angela M.; Uckert, Wolfgang; Wohlleber, Dirk; Schiemann, Matthias; Stemmer, Kerstin; Heikenwälder, Mathias; Busch, Dirk H.; Richter, Günther; Mann, Matthias; Protzer, Ulrike: T Cells Engineered to Express a T-Cell Receptor Specific for Glypican-3 to Recognize and Kill Hepatoma Cells In Vitro and in Mice. Gastroenterology 149 (4), 2015, 1042-1052 more…
  • Flossdorf, Michael; Rössler, Jens; Buchholz, Veit R; Busch, Dirk H; Höfer, Thomas: CD8+ T cell diversification by asymmetric cell division. Nature Immunology 16 (9), 2015, 891-893 more…
  • Günther, Patrick S.; Peper, Janet K.; Faist, Benjamin; Kayser, Simone; Hartl, Lena; Feuchtinger, Tobias; Jahn, Gerhard; Neuenhahn, Michael; Busch, Dirk H.; Stevanović, Stefan; Dennehy, Kevin M.: Identification of a Novel Immunodominant HLA-B*07. Journal of Immunotherapy 38 (7), 2015, 267-275 more…
  • Loregger, A.; Grandl, M.; Mejias-Luque, R.; Allgauer, M.; Degenhart, K.; Haselmann, V.; Oikonomou, C.; Hatzis, P.; Janssen, K.-P.; Nitsche, U.; Gradl, D.; van den Broek, O.; Destree, O.; Ulm, K.; Neumaier, M.; Kalali, B.; Jung, A.; Varela, I.; Schmid, R. M.; Rad, R.; Busch, D. H.; Gerhard, M.: The E3 ligase RNF43 inhibits Wnt signaling downstream of mutated  -catenin by sequestering TCF4 to the nuclear membrane. Science Signaling 8 (393), 2015, ra90-ra90 more…
  • Loregger, Anke; Grandl, Martina; Mejías-Luque, Raquel; Allgäuer, Michael; Degenhart, Kathrin; Haselmann, Verena; Oikonomou, Christina; Hatzis, Pantelis; Janssen, Klaus-Peter; Nitsche, Ulrich; Gradl, Dietmar; van den Broek, Olaf; Destree, Olivier; Ulm, Kurt; Neumaier, Michael; Kalali, Behnam; Jung, Andreas; Varela, Ignacio; Schmid, Roland M.; Rad, Roland; Busch, Dirk H.; Gerhard, Markus: The E3 ligase RNF43 inhibits Wnt signaling downstream of mutated β-catenin by sequestering TCF4 to the nuclear membrane. Science Signaling 8 (393), 2015, ra90-ra90 more…
  • Sommermeyer, D; Hudecek, M; Kosasih, P L; Gogishvili, T; Maloney, D G; Turtle, C J; Riddell, S R: Chimeric antigen receptor-modified T cells derived from defined CD8+ and CD4+ subsets confer superior antitumor reactivity in vivo. Leukemia 30 (2), 2015, 492-500 more…

2014

  • Berger, C.; Sommermeyer, D.; Hudecek, M.; Berger, M.; Balakrishnan, A.; Paszkiewicz, P. J.; Kosasih, P. L.; Rader, C.; Riddell, S. R.: Safety of Targeting ROR1 in Primates with Chimeric Antigen Receptor-Modified T Cells. Cancer Immunology Research 3 (2), 2014, 206-216 more…
  • Bleakley, Marie; Heimfeld, Shelly; Jones, Lori A.; Turtle, Cameron; Krause, Diane; Riddell, Stanley R.; Shlomchik, Warren: Engineering Human Peripheral Blood Stem Cell Grafts that Are Depleted of Naïve T Cells and Retain Functional Pathogen-Specific Memory T Cells. Biology of Blood and Marrow Transplantation 20 (5), 2014, 705-716 more…
  • Graef, Patricia; Buchholz, Veit R.; Stemberger, Christian; Flossdorf, Michael; Henkel, Lynette; Schiemann, Matthias; Drexler, Ingo; Höfer, Thomas; Riddell, Stanley R.; Busch, Dirk H.: Serial Transfer of Single-Cell-Derived Immunocompetence Reveals Stemness of CD8+ Central Memory T Cells. Immunity 41 (1), 2014, 116-126 more…
  • Hudecek, M.; Sommermeyer, D.; Kosasih, P. L.; Silva-Benedict, A.; Liu, L.; Rader, C.; Jensen, M. C.; Riddell, S. R.: The Nonsignaling Extracellular Spacer Domain of Chimeric Antigen Receptors Is Decisive for In Vivo Antitumor Activity. Cancer Immunology Research 3 (2), 2014, 125-135 more…
  • Paszkiewicz, Paulina Joanna: Development of a truncated EGFR marker as a safeguard for adoptive T cell therapy. Dissertation, 2014 more…
  • Pollack, Seth M; Jones, Robin L; Farrar, Erik A; Lai, Ivy P; Lee, Sylvia M; Cao, Jianhong; Pillarisetty, Venu G; Hoch, Benjamin L; Gullett, Ashley; Bleakley, Marie; Conrad, Ernest U; Eary, Janet F; Shibuya, Kendall C; Warren, Edus H; Carstens, Jason N; Heimfeld, Shelly; Riddell, Stanley R; Yee, Cassian: Tetramer guided, cell sorter assisted production of clinical grade autologous NY-ESO-1 specific CD8+ T cells. Journal for ImmunoTherapy of Cancer 2 (1), 2014 more…
  • Riddell, Stanley R.; Sommermeyer, Daniel; Berger, Carolina; Liu, Lingfeng (Steven); Balakrishnan, Ashwini; Salter, Alex; Hudecek, Michael; Maloney, David G.; Turtle, Cameron J.: Adoptive Therapy With Chimeric Antigen Receptor–Modified T Cells of Defined Subset Composition. The Cancer Journal 20 (2), 2014, 141-144 more…
  • Shibuya, Kendall C.; Goel, Vikas K.; Xiong, Wei; Sham, Jonathan G.; Pollack, Seth M.; Leahy, Allison M.; Whiting, Samuel H.; Yeh, Matthew M.; Yee, Cassian; Riddell, Stanley R.; Pillarisetty, Venu G.: Pancreatic Ductal Adenocarcinoma Contains an Effector and Regulatory Immune Cell Infiltrate that Is Altered by Multimodal Neoadjuvant Treatment. PLoS ONE 9 (5), 2014, e96565 more…
  • Stemberger, C.; Graef, P.; Odendahl, M.; Albrecht, J.; Dossinger, G.; Anderl, F.; Buchholz, V. R.; Gasteiger, G.; Schiemann, M.; Grigoleit, G. U.; Schuster, F. R.; Borkhardt, A.; Versluys, B.; Tonn, T.; Seifried, E.; Einsele, H.; Germeroth, L.; Busch, D. H.; Neuenhahn, M.: Lowest numbers of primary CD8+ T cells can reconstitute protective immunity upon adoptive immunotherapy. Blood 124 (4), 2014, 628-637 more…

2013

  • Buchholz, V. R.; Flossdorf, M.; Hensel, I.; Kretschmer, L.; Weissbrich, B.; Graf, P.; Verschoor, A.; Schiemann, M.; Hofer, T.; Busch, D. H.: Disparate Individual Fates Compose Robust CD8+ T Cell Immunity. Science 340 (6132), 2013, 630-635 more…
  • Hudecek, M.; Lupo-Stanghellini, M.-T.; Kosasih, P. L.; Sommermeyer, D.; Jensen, M. C.; Rader, C.; Riddell, S. R.: Receptor Affinity and Extracellular Domain Modifications Affect Tumor Recognition by ROR1-Specific Chimeric Antigen Receptor T Cells. Clinical Cancer Research 19 (12), 2013, 3153-3164 more…
  • Jensen, Michael C.; Riddell, Stanley R.: Design and implementation of adoptive therapy with chimeric antigen receptor-modified T cells. Immunological Reviews 257 (1), 2013, 127-144 more…
  • Nauerth, M.; Weissbrich, B.; Knall, R.; Franz, T.; Dossinger, G.; Bet, J.; Paszkiewicz, P. J.; Pfeifer, L.; Bunse, M.; Uckert, W.; Holtappels, R.; Gillert-Marien, D.; Neuenhahn, M.; Krackhardt, A.; Reddehase, M. J.; Riddell, S. R.; Busch, D. H.: TCR-Ligand koff Rate Correlates with the Protective Capacity of Antigen-Specific CD8+ T Cells for Adoptive Transfer. Science Translational Medicine 5 (192), 2013, 192ra87-192ra87 more…
  • Neuenhahn, Michael; Busch, Dirk H.: Whole-Body Anatomy of Human T Cells. Immunity 38 (1), 2013, 10-12 more…

2012

  • Stemberger, Christian; Dreher, Stefan; Tschulik, Claudia; Piossek, Christine; Bet, Jeannette; Yamamoto, Tori N.; Schiemann, Matthias; Neuenhahn, Michael; Martin, Klaus; Schlapschy, Martin; Skerra, Arne; Schmidt, Thomas; Edinger, Matthias; Riddell, Stanley R.; Germeroth, Lothar; Busch, Dirk H.: Novel Serial Positive Enrichment Technology Enables Clinical Multiparameter Cell Sorting. PLoS ONE 7 (4), 2012, e35798 more…