RG T cell Therapy
- adoptive transfer of T cells
- virus specific T cells
- CAR T cells
Manufacturing of CAR T cells
Therapy with CAR T-cell is one of the most promising developments in the last years. In an in-house GMP lab a multi-disciplinary team of Medicine 5 personnel performs manufacturing and quality control of CAR T cells.
GMP-Lab
The research group of Dr. Michael Aigner is engaged in the exploration and understanding of new cellular therapies; Research focus is the enhancement and development of T-cell immunotherapy.
Lab Members
- Dr. Michael Aigner (PI)
- Luisa Albert (PTA)
- Lina Meretuk (MSc)
- Stephanie Moi (MTA)
- Stefanie Schaffer (MTA)
- Heidi Spreitzer (MTA)
Adoptive T-Cell Transfer
Adoptive T-cell therapy aims the elimination of malignant cells by transferring immune cells. An impressive confirmation of the efficacy of transferred lymphocytes is provided in allogeneic stem cell transplantation (SCT) in form of either bone marrow transplantation or the transfer of collected stem cells by leukapheresis after G-CSF mobilization of the allogeneic donor. In acute and especially chronic myeloid leukemia (CML) the graft-versus-leukemia effect - which is predominantly mediated by T-lymphocytes - is the central principle of the therapeutic SCT.
The first clinical trials of adoptive lymphocyte transfer indeed show a therapeutic effect on the tumor growth. However, the therapeutic efficacy is limited so far, so that an improvement of existing or the development of completely new approaches is needed.
In addition, T lymphocytes are critically involved in the control of viral diseases. Particularly in the first period after SCT patients often do not show sufficient immune protection which leads to the development of many serious and difficult-to-treat infections with viruses as Cytomegalovirus (CMV) or Epstein-Barr viruses (EBV).
Our aim is the selection and expansion of beneficial T lymphocytes under Good Manufacturing Practice (GMP) conditions, which allows us the application of these cellular products in clinical trials. Additionally, we are working on new strategies to improve the antigen-specificity and the function of the in vitro expanded T lymphocytes.
We were able to develop a protocol that allows us to collect, expand and analyze CMV/EBV-reactive T cells for the prevention and treatment of viral disease after SCT in the context of a clinical trial (Phase I/IIa) and expanding this process for other viral infections.
Our long term goal is the improvement of adoptive T-cell therapy and that our results will form the basis for a new clinical trial of adoptive T-lymphocyte therapy in patients with malignant diseases.
Selected publications
CD19-Targeted CAR T Cells in Refractory Systemic Lupus Erythematosus. Mougiakakos D, Krönke G, Völkl S, Kretschmann S, Aigner M, Kharboutli S, Böltz S, Manger B, Mackensen A, Schett G. N Engl J Med. 2021 Aug 5;385(6):567-569. doi: 10.1056/NEJMc2107725. PMID: 34347960 No abstract available.
Reconstitution of EBV-directed T cell immunity by adoptive transfer of peptide-stimulated T cells in a patient after allogeneic stem cell transplantation for AITL. Lammoglia Cobo MF, Ritter J, Gary R, Seitz V, Mautner J, Aigner M, Völkl S, Schaffer S, Moi S, Seegebarth A, Bruns H, Rösler W, Amann K, Büttner-Herold M, Hennig S, Mackensen A, Hummel M, Moosmann A, Gerbitz A. PLoS Pathog. 2022 Apr 22;18(4):e1010206. doi: 10.1371/journal.ppat.1010206. eCollection 2022 Apr. PMID: 35452490 Free PMC article.
Impact of collection programs for the generation of monocyte apheresis products on product quality and composition as starting material for the generation of cellular therapeutics. Pfeiffer H, Völkl S, Gary R, Mackensen A, Achenbach S, Strasser E, Aigner M. Transfusion. 2018 Sep;58(9):2175-2183. doi: 10.1111/trf.14817. PMID: 30204947
Clinical-grade generation of peptide-stimulated CMV/EBV-specific T cells from G-CSF mobilized stem cell grafts. Gary R, Aigner M, Moi S, Schaffer S, Gottmann A, Maas S, Zimmermann R, Zingsem J, Strobel J, Mackensen A, Mautner J, Moosmann A, Gerbitz A. J Transl Med. 2018 May 9;16(1):124. doi: 10.1186/s12967-018-1498-3. PMID: 29743075 Free PMC article.
T lymphocytes can be effectively recruited for ex vivo and in vivo lysis of AML blasts by a novel CD33/CD3-bispecific BiTE antibody construct. Aigner M, Feulner J, Schaffer S, Kischel R, Kufer P, Schneider K, Henn A, Rattel B, Friedrich M, Baeuerle PA, Mackensen A, Krause SW. Leukemia. 2013 Apr 27(5): 1107-15. doi: 10.1038/leu.2012.341. Epub 2012 Nov 26. PMID: 23178753
Effective elimination of acute myeloid leukemic cells by recombinant bispecific antibody derivatives directed against CD33 and CD16. Singer H, Kellner C, Lanig H, Aigner M, Stockmeyer B, Oduncu F, Schwemmlein M, Stein C, Mentz K, Mackensen A, Fey GH. J Immunother. 2010 Jul-Aug;33(6):599-608. doi: 10.1097/CJI.0b013e3181dda225. PMID: 20551837
Successful treatment of COVID-19 infection with convalescent plasma in B-cell-depleted patients may promote cellular immunity. Kremer AE, Kremer AN, Willam C, Völkl S, Verhagen J, Achenbach S, van der Meijden ED, Lang V, Aigner M, Maier C, Tenbusch M, Korn K, Lutzny-Geier G, Spoerl S, Strauß R, Vetter M, Überla K, Neurath MF, Mackensen A, Schiffer M, Hackstein H. Eur J Immunol. 2021 Oct;51(10):2478-2484. doi: 10.1002/eji.202149277. Epub 2021 Sep 3. PMID: 34350584 Free PMC article.
Upregulation of CCR4 in activated CD8+ T cells indicates enhanced lung homing in patients with severe acute SARS-CoV-2 infection. Spoerl S, Kremer AN, Aigner M, Eisenhauer N, Koch P, Meretuk L, Löffler P, Tenbusch M, Maier C, Überla K, Heinzerling L, Frey B, Lutzny-Geier G, Winkler TH, Krönke G, Vetter M, Bruns H, Neurath MF, Mackensen A, Kremer AE, Völkl S. Eur J Immunol. 2021 Jun;51(6):1436-1448. doi: 10.1002/eji.202049135. Epub 2021 Apr 19. PMID: 33784417 Free PMC article. Clinical Trial.
Human CD4+ T cells specific for dominant epitopes of SARS-CoV-2 Spike and Nucleocapsid proteins with therapeutic potential. Verhagen J, van der Meijden ED, Lang V, Kremer AE, Völkl S, Mackensen A, Aigner M, Kremer AN. Clin Exp Immunol. 2021 Sep;205(3):363-378. doi: 10.1111/cei.13627. Epub 2021 Jun 29. PMID: 34061349 Free PMC article.
Selective PRMT5 Inhibitors Suppress Human CD8+ T Cells by Upregulation of p53 and Impairment of the AKT Pathway Similar to the Tumor Metabolite MTA. Strobl CD, Schaffer S, Haug T, Völkl S, Peter K, Singer K, Böttcher M, Mougiakakos D, Mackensen A, Aigner M. Mol Cancer Ther. 2020 Feb;19(2):409-419. doi: 10.1158/1535-7163.MCT-19-0189. Epub 2019 Nov 11. PMID: 31712395
The Oncometabolite 5'-Deoxy-5'-Methylthioadenosine Blocks Multiple Signaling Pathways of NK Cell Activation. Jacobs B, Schlögl S, Strobl CD, Völkl S, Stoll A, Mougiakakos D, Malmberg KJ, Mackensen A, Aigner M. Front Immunol. 2020 Oct 6;11:2128. doi: 10.3389/fimmu.2020.02128. eCollection 2020. PMID: 33123121 Free PMC article.
Suppressive effects of tumor cell-derived 5'-deoxy-5'-methylthioadenosine on human T cells. Henrich FC, Singer K, Poller K, Bernhardt L, Strobl CD, Limm K, Ritter AP, Gottfried E, Völkl S, Jacobs B, Peter K, Mougiakakos D, Dettmer K, Oefner PJ, Bosserhoff AK, Kreutz MP, Aigner M, Mackensen A. Oncoimmunology. 2016 Jun 10;5(8):e1184802. doi: 10.1080/2162402X.2016.1184802. eCollection 2016 Aug. PMID: 27622058 Free PMC article.
Warburg phenotype in renal cell carcinoma: high expression of glucose-transporter 1 (GLUT-1) correlates with low CD8(+) T-cell infiltration in the tumor. Singer K, Kastenberger M, Gottfried E, Hammerschmied CG, Büttner M, Aigner M, Seliger B, Walter B, Schlösser H, Hartmann A, Andreesen R, Mackensen A, Kreutz M. Int J Cancer. 2011 May 1;128(9):2085-95. doi: 10.1002/ijc.25543. PMID: 20607826
Visualizing Single-Cell Secretion Dynamics with Single-Protein Sensitivity. McDonald MP, Gemeinhardt A, König K, Piliarik M, Schaffer S, Völkl S, Aigner M, Mackensen A, Sandoghdar V. Nano Lett. 2018 Jan 10;18(1):513-519. doi: 10.1021/acs.nanolett.7b04494. Epub 2017 Dec 19. PMID: 29227108
In situ analysis of the antigen-processing machinery in acute myeloid leukaemic blasts by tissue microarray. Hoves S, Aigner M, Pfeiffer C, Laumer M, Obermann EC, Mackensen A. Leukemia. 2009 May;23(5):877-85. doi: 10.1038/leu.2008.391. Epub 2009 Jan 15. PMID: 19148137
