Regenerative Immune Therapies Applied


Increased risks for infections, cancer and morbidity are associated with changes in immune function. Several factors such as chronological age, gender, infections with human cytomegalovirus (HCMV) and intense pre- and post-transplantation regimens have been associated with the process of immune-senescence. Our laboratory explores the targeted genetic manipulation of cellular components of the immune system to be applied in the immune-oncology field and also to overcome chronic infections and immune-senescence. In order to achieve these goals, we have:

  • A long-standing experience with ex vivo genetic reprogramming of monocytes with lentiviral vectors for generation of dendritic cells in vivo.
  • Developed T cells expressing chimeric antigen receptors (CAR) targeted against chronic herpes infections.
  • Established humanized mouse models for preclinical in vivo testing of new immune therapies.

Research Focus

1. Lentiviral vectors and monocyte reprogramming for regenerative immune therapies against cancer and HCMV (Current funding: Rebirth Excellence Cluster, Collaborative Research Center 738 and Else Kröner-Fresenius Stiftung. Past funding: Deutsche Krebshilfe, Bundesministerium für Bildung und Forschung).

Lentiviral vectors are highly effective and safe in the clinics for gene replacement and for engineering T cells. We designed and generated a collection of monocistronic, bicistronic and tricistronic vectors expressing tumor antigens, signaling molecules, cytokines and stimulatory ligands for immune therapy applications. We have a long-standing experience with ex vivo lentiviral reprogramming of monocytes, which become equipped to autonomously self-differentiate into potent dendritic cells in vivo. Integrase-defective lentiviral vectors (IDLVs) are safer and effective to generate iDCs. Their productions were validated under state-of-the-art Good Manufacturing Practice (GMP) and are in the translation to the first clinical trials as adjuvant treatments of leukemia or melanoma patients and to protect post-transplant patients against HCMV reactivations. As a first-in-man advanced immune therapeutic medicinal product (ATMP), iDCs can effectively promote new repertoires of cellular and antibody responses. The Paul-Ehrlich-Institut (PEI), that regulates the approval of clinical trials in Germany, provided us with recommendations for production, quality, non-clinical pharm-tox and clinical study design. In collaboration with the Hannover Clinical Trial Center (HCTC) and the MHH Cell Therapies Centre (CTC) we are preparing a multicenter phase I/IIa clinical trial to immunize leukemia patients after standard therapy and during remission.


2. Engineered chimeric antigen receptor-expressing T cells (CAR-T) against herpes virus infections (Funding: German Center for Infections Research – DZIF).

HCMV can cause morbidity and mortality to immune compromised patients after transplantations. Although antiviral drugs are available, toxicities and drug resistance remain problematic. Memory T cells from patients or HLA-matched donors can be expanded in vitro and used adoptively to contain these infections. But this approach is inefficient when highly specific memory T cells are lacking. In collaboration with Dr. Malcolm Brenner and Dr. Cliona Rooney (Baylor College of Medicine), we developed CAR-T cells targeted against HCMV. These CAR-T cells have been validated in vitro and we are now exploring gene editing approaches with the CRISPR/Cas systems for their further optimizations. This concept is been expanded to other types of herpes viruses.


3. Humanized mouse models with human T and B cell immune responses to study human infections and to test new therapies in vivo (Funding: German Center for Infections Research –DZIF).

One very important aspect for development of new immune therapies is their preclinical in vivo testing. In order to replicate the human adaptive responses in vivo, we have established humanized mouse models. For this, immune deficient mice are transplanted with hematopoietic stem cells (HSCs). Five to six months later, mature human T and B cells can be observed. We are currently optimizing these models with new technologies, such that the human immune reconstitutions can develop faster and more consistently. We demonstrated that iDCs applied into NOD/Rag1null/IL2Rγnull (NRG) mice after human HSC transplantation accelerated de novo development human antigen-specific T cell immunity, tolerogenic T cells (Tregs), mature B cells and human antibody responses (IgM and IgG). These humanized endogenously regenerated systems (“HERS”) have a broad application for the understanding of human in vivo immune reconstitution. We also explored humanized mice to characterize the in vivo spread and dynamics of HCMV and EBV infections using non-invasive bioluminescence imaging analyses coupled with computerized tomography scans. In collaboration with Dr. Wolfgang Hammerschmidt and Dr. Reinhold Zeidler (Helmholtz Centre for Infection, Munich) we are testing virus-like particles and monoclonal antibodies against EBV infections in humanized mice. We also collaborate with several groups interested in utilizing humanized mice to test new vaccines, monoclonal antibodies and engineered cells in vivo.


  • Dr. Heiko von der Leyen (Rebirth Unit 10.6, HCTC, MHH), Dr. Arnold Ganser (Hem/Onc, MHH), Dr. Ulrike Köhl (IFB-TX, MHH), Dr. Michael Schmitt (Hem/Onc, Heidelberg): Clinical development of iDCs.
  • Dr. Axel Schambach (Rebirth Unit 6.2, Exp. Hematol, MHH): Development of novel vectors.
  • Dr. Rainer Blasczyk (TM, MHH), Dr. Constanca Figueiredo (Rebirth Unit 6.3, MHH): HLA engineering of HSC grafts in humanized mice.
  • Dr. Katharina Seewald, Dr. Armin Braun and Dr. Henning Weigt (Rebirth Unit 9.4, ITEM-Fraunhofer): Pharm-tox analyses in humanized mice.
  • Dr. Ralf Gutzmer (Dermat. MHH): Melanoma immune therapies.
  • Dr. Martin Messerle (Virol., MHH): HCMV infection.
  • Dr. Wolfgang Hammerschmidt and Dr.Reinhard Zeidler (HZI, Munich): EBV infection.
  • Dr. Carlos Guzman (HZI, Braunschweig): Use of humanized mice for vaccinology.

International Collaborations

  • Dr. Malcolm Brenner and Dr. Cliona Rooney (Baylor College of Medicine, Houston, USA): CAR-T cells against herpes virus infections.
  • Dr. Farzin Farzaneh (King’s College London): Production of GMP-grade lentiviral vectors.
  • Dr. Nori Kasahara (University of Miami): HLA-Engineering of grafts.


  • H. Olbrich (medical student): 2017 DZIF award best poster.
  • H. Olbrich and C. Slabik (medical students): 2016 DZIF-Strucmed fellowships.
  • R. Stripecke (PI): 2015 DFG award funding for sabbatical at Baylor College of Medicine.
  • S. Theobald (PhD student): 2015 REGSCI PhD fellowship.
  • D. Queiros (PhD student, Portugal): 2015 DAAD fellowship (REGSCI, MHH).
  • V. Volk (PhD student from Belarus): 2014 DAAD fellowship (ZIB, MHH).
  • C. Deves Roth (post-doc, University of Porto Alegre, past alumni): 2014 fellowship from the Science without Borders from the Brazilian government.
  • C. Govayets (visiting PhD student from Free University Belgium): 2014 fellowship from the Fund for Scientific Research, Belgium.
  • M. Pinho (visiting master student University of Sao Paulo): 2014 fellowship from FAPESP, Brazil.


  • PhD programme ‘Regenerative Sciences’: Antigen Presenting Cells
  • PhD programme ‘Molecular Medicine’: Viral vectors for gene transfer in vitro and in vivo
  • PhD programme ‘Infectious Biology’: Recombinant vaccines
  • TRAIN Niedersachsen ‘Post-doctoral programme: Development and in vivo testing of ATMPs

Self-differentiation of induced dendritic cells (iDCs)

A humanized mouse infected with Epstein Barr Virus (EBV) and developing tumors


2013 - ongoing


Stripecke R, Muenz C, Schuringa JJ, Bissig K, Soper B, Meeham T, Yao L, Di Santo J, Brehm M, Rodriguez E, Wege AK, Bonnet D, Guionaud S, Howard K, Kitchen S, Klein F, Saeb-Parsy K, Sam J, Deep Sharma A, Trumpp A, Trusolino L, Bult C, Shultz L, Innovations, challenges, and minimal inforation for standardization of humanized mice. EMBO Molecular Medicine. 2020/05/14 e8662


Paehler Vor der Nolte A, Chodisetti G, Yuan Z, Busch F, Riederer B, Luo M, Yu Y, Menon MB, Schneider A, Stripecke R, Nikolovska K, Yeruva S, Seidler U. Na(+) /H(+) exchanger NHE1 and NHE2 have opposite effects on migration velocity in rat gastric surface cells. J Cell Physiol. 2016/12/27 ed2017. p. 1669-80.

Olbrich H, Slabik C, Stripecke R. Reconstructing the immune system with lentiviral vectors. Virus Genes. 2017/07/27 ed2017. p. 723-32.

Sundarasetty B, Volk V, Theobald SJ, Rittinghausen S, Schaudien D, Neuhaus V, Figueiredo C, Schneider A, Gerasch L, Mucci A, Moritz T, von Kaisenberg C, Spineli LM, Sewald K, Braun A, Weigt H, Ganser A, Stripecke R. Human Effector Memory T Helper Cells Engage with Mouse Macrophages and Cause Graft-versus-Host-Like Pathology in Skin of Humanized Mice Used in a Nonclinical Immunization Study. Am J Pathol. 2017/04/23 ed2017. p. 1380-98.

Volk V, Reppas AI, Robert PA, Spineli LM, Sundarasetty BS, Theobald SJ, Schneider A, Gerasch L, Deves Roth C, Klöss S, Koehl U, Kaisenberg Cv, Figueiredo C, Hatzikirou H, Meyer-Hermann M, Stripecke R. Multidimensional Analysis Integrating Human T-Cell Signatures in Lymphatic Tissues with Sex of Humanized Mice for Prediction of Responses after Dendritic Cell Immunization. Front Immunol2017.


Stripecke R, Gouttefangeas C, Förster I. 1st EMBL/DFG Women in Science Network Conference Heidelberg 2016. Eur J Immunol2016. p. 2492-5.

Stripecke R. Leukemias and bones: humanizing the niche in mice. Blood. 2016/12/23 ed2016. p. 2874-5.

Volk V, Schneider A, Spineli LM, Grosshennig A, Stripecke R. The gender gap: discrepant human T-cell reconstitution after cord blood stem cell transplantation in humanized female and male mice. Bone Marrow Transplant. 2016;51(4):596-7.

Pinho MP, Sundarasetty BS, Bergami-Santos PC, Steponavicius-Cruz K, Ferreira AK, Stripecke R, Barbuto JA. Dendritic-tumor cell hybrids induce tumor-specific immune responses more effectively than the simple mixture of dendritic and tumor cells. Cytotherapy. 2016;18(4):570-80.

Low HZ, Ahrenstorf G, Pommerenke C, Habermann N, Schughart K, Ordonez D, Stripecke R, Wilk E, Witte T. TLR8 regulation of LILRA3 in monocytes is abrogated in human immunodeficiency virus infection and correlates to CD4 counts and virus loads. Retrovirology. 2016;13:15.


Sundarasetty BS, Chan L, Darling D, Giunti G, Farzaneh F, Schenck F, Naundorf S, Kuehlcke K, Ruggiero E, Schmidt M, von Kalle C, Rothe M, Hoon DS, Gerasch L, Figueiredo C, Koehl U, Blasczyk R, Gutzmer R, Stripecke R. Lentivirus-Induced 'Smart' Dendritic Cells: Pharmacodynamics and Gmp-Compliant Production for Immunotherapy against Trp2-Positive Melanoma. Gene Ther. 2015;22(9):707-20. Epub 2015/05/13.

Sundarasetty BS, Kloess S, Oberschmidt O, Naundorf S, Kuehlcke K, Daenthanasanmak A, Gerasch L, Figueiredo C, Blasczyk R, Ruggiero E, Fronza R, Schmidt M, von Kalle C, Rothe M, Ganser A, Koehl U, Stripecke R. Generation of Lentivirus-Induced Dendritic Cells under Gmp-Compliant Conditions for Adaptive Immune Reconstitution against Cytomegalovirus after Stem Cell Transplantation. J Transl Med. 2015;13:240. Epub 2015/07/23.

Volk V, Schneider A, Spineli LM, Grosshennig A, (1, 2) R. The Gender Gap: Discrepant human T cell reconstitution after cord blood stem cell transplantation in humanized female and male mice. Bone Marrow Transplantation, in press.

Daenthanasanmak A, Salguero G, Sundarasetty BS, Waskow C, Cosgun KN, Guzman CA, Riese P, Gerasch L, Schneider A, Ingendoh A, Messerle M, Gabaev I, Woelk B, Ruggiero E, Schmidt M, von Kalle C, Figueiredo C, Eiz-Vesper B, von Kaisenberg C, Ganser A, Stripecke R. Engineered Dendritic Cells from Cord Blood and Adult Blood Accelerate Effector T Cell Immune Reconstitution against Hcmv. Mol Ther Methods Clin Dev. 2015;1:14060.


Salguero G, Daenthanasanmak A, Munz C, Raykova A, Guzman CA, Riese P, Figueiredo C, Langer F, Schneider A, Macke L, Sundarasetty BS, Witte T, Ganser A, Stripecke R. Dendritic Cell-Mediated Immune Humanization of Mice: Implications for Allogeneic and Xenogeneic Stem Cell Transplantation. J Immunol. 2014;192(10):4636-47.

Tischer S, Dieks D, Sukdolak C, Bunse C, Figueiredo C, Immenschuh S, Borchers S, Stripecke R, Maecker-Kolhoff B, Blasczyk R, Eiz-Vesper B. Evaluation of Suitable Target Antigens and Immunoassays for High-Accuracy Immune Monitoring of Cytomegalovirus and Epstein-Barr Virus-Specific T Cells as Targets of Interest in Immunotherapeutic Approaches. J Immunol Methods. 2014;408:101-13.

Stripecke R. Lentivirus-Induced Dendritic Cells (Idc) for Immune-Regenerative Therapies in Cancer and Stem Cell Transplantation. Biomedicines. 2014;2(3):229.

Schlahsa L, Zhang H, Battermann A, Verboom M, Immenschuh S, Eiz-Vesper B, Stripecke R, Engelmann K, Blasczyk R, Figueiredo C. Semaphorin 3a Alters Endothelial Cell Immunogenicity by Regulating Class Ii Transactivator Activity Circuits. Transfusion. 2014;54(8):1961-70.


Low HZ, Reuter S, Topperwien M, Dankenbrink N, Peest D, Kabalak G, Stripecke R, Schmidt RE, Matthias T, Witte T. Association of the Lilra3 Deletion with B-Nhl and Functional Characterization of the Immunostimulatory Molecule. PLoS One. 2013;8(12):e81360.

Lam P, Khan G, Stripecke R, Hui KM, Kasahara N, Peng KW, Guinn BA. The Innovative Evolution of Cancer Gene and Cellular Therapies. Cancer Gene Ther. 2013;20(3):141-9.

Sundarasetty BS, Singh VK, Salguero G, Geffers R, Rickmann M, Macke L, Borchers S, Figueiredo C, Schambach A, Gullberg U, Provasi E, Bonini C, Ganser A, Woelfel T, Stripecke R. Lentivirus-Induced Dendritic Cells for Immunization against High-Risk Wt1(+) Acute Myeloid Leukemia. Hum Gene Ther. 2013;24(2):220-37.

Rickmann M, Macke L, Sundarasetty BS, Stamer K, Figueiredo C, Blasczyk R, Heuser M, Krauter J, Ganser A, Stripecke R. Monitoring Dendritic Cell and Cytokine Biomarkers During Remission Prior to Relapse in Patients with Flt3-Itd Acute Myeloid Leukemia. Ann Hematol. 2013;92(8):1079-90.

Wolf S, Rudolph C, Morgan M, Busche G, Salguero G, Stripecke R, Schlegelberger B, Baum C, Modlich U. Selection for Evi1 Activation in Myelomonocytic Leukemia Induced by Hyperactive Signaling through Wild-Type Nras. Oncogene. 2013;32(25):3028-38.

2006 - 2012


Pincha M, Sundarasetty BS, Salguero G, Gutzmer R, Garritsen H, Macke L, Schneider A, Lenz D, Figueiredo C, Blasczyk R, Ruggiero E, Schmidt M, von Kalle C, Puff C, Modlich U, von der Leyen H, Wicke DC, Ganser A, Stripecke R. Identity, Potency, in Vivo Viability, and Scaling up Production of Lentiviral Vector-Induced Dendritic Cells for Melanoma Immunotherapy. Hum Gene Ther Methods. 2012;23(1):38-55.

Daenthanasanmak A, Salguero G, Borchers S, Figueiredo C, Jacobs R, Sundarasetty BS, Schneider A, Schambach A, Eiz-Vesper B, Blasczyk R, Weissinger EM, Ganser A, Stripecke R. Integrase-Defective Lentiviral Vectors Encoding Cytokines Induce Differentiation of Human Dendritic Cells and Stimulate Multivalent Immune Responses in Vitro and in Vivo. Vaccine. 2012;30(34):5118-31.


Rickmann M, Krauter J, Stamer K, Heuser M, Salguero G, Mischak-Weissinger E, Ganser A, Stripecke R. Elevated Frequencies of Leukemic Myeloid and Plasmacytoid Dendritic Cells in Acute Myeloid Leukemia with the Flt3 Internal Tandem Duplication. Ann Hematol. 2011;90(9):1047-58.

Pincha M, Salguero G, Wedekind D, Sundarasetty BS, Lin A, Kasahara N, Brugman MH, Jirmo AC, Modlich U, Gutzmer R, Busche G, Ganser A, Stripecke R. Lentiviral Vectors for Induction of Self-Differentiation and Conditional Ablation of Dendritic Cells. Gene Ther. 2011;18(8):750-64.

Salguero G, Sundarasetty BS, Borchers S, Wedekind D, Eiz-Vesper B, Velaga S, Jirmo AC, Behrens G, Warnecke G, Knofel AK, Blasczyk R, Mischak-Weissinger E, Ganser A, Stripecke R. Preconditioning Therapy with Lentiviral Vector-Programmed Dendritic Cells Accelerates the Homeostatic Expansion of Antigen-Reactive Human T Cells in Nod.Rag1-/-.Il-2rgammac-/- Mice. Hum Gene Ther. 2011;22(10):1209-24.


Pincha M, Sundarasetty BS, Stripecke R. Lentiviral Vectors for Immunization: An Inflammatory Field. Expert Rev Vaccines. 2010;9(3):309-21.

Jirmo AC, Koya RC, Sundarasetty BS, Pincha M, Yu GY, Lai M, Bakshi R, Schlaphoff V, Grabowski J, Behrens G, Wedemeyer H, Stripecke R. Monocytes Transduced with Lentiviral Vectors Expressing Hepatitis C Virus Non-Structural Proteins and Differentiated into Dendritic Cells Stimulate Multi-Antigenic Cd8(+) T Cell Responses. Vaccine. 2010;28(4):922-33.


Stripecke R. Lentiviral Vector-Mediated Genetic Programming of Mouse and Human Dendritic Cells. Methods Mol Biol. 2009;506:139-58.


Kochling J, Prada J, Bahrami M, Stripecke R, Seeger K, Henze G, Wittig B, Schmidt M. Anti-Tumor Effect of DNA-Based Vaccination and Dslim Immunomodulatory Molecules in Mice with Ph+ Acute Lymphoblastic Leukaemia. Vaccine. 2008;26(36):4669-75. Epub 2008/07/22.

Sarafian T, Montes C, Harui A, Beedanagari SR, Kiertscher S, Stripecke R, Hossepian D, Kitchen C, Kern R, Belperio J, Roth MD. Clarifying Cb2 Receptor-Dependent and Independent Effects of Thc on Human Lung Epithelial Cells. Toxicol Appl Pharmacol. 2008;231(3):282-90.

Cheng JC, Kinjo K, Judelson DR, Chang J, Wu WS, Schmid I, Shankar DB, Kasahara N, Stripecke R, Bhatia R, Landaw EM, Sakamoto KM. Creb Is a Critical Regulator of Normal Hematopoiesis and Leukemogenesis. Blood. 2008;111(3):1182-92. Epub 2007/11/03.


Koya RC, Kimura T, Ribas A, Rozengurt N, Lawson GW, Faure-Kumar E, Wang HJ, Herschman H, Kasahara N, Stripecke R. Lentiviral Vector-Mediated Autonomous Differentiation of Mouse Bone Marrow Cells into Immunologically Potent Dendritic Cell Vaccines. Mol Ther. 2007;15(5):971-80.

Kimura T, Koya RC, Anselmi L, Sternini C, Wang HJ, Comin-Anduix B, Prins RM, Faure-Kumar E, Rozengurt N, Cui Y, Kasahara N, Stripecke R. Lentiviral Vectors with Cmv or Mhcii Promoters Administered in Vivo: Immune Reactivity Versus Persistence of Expression. Mol Ther. 2007;15(7):1390-9.


Koya RC, Weber JS, Kasahara N, Lau R, Villacres MC, Levine AM, Stripecke R. Making Dendritic Cells from the inside Out: Lentiviral Vector-Mediated Gene Delivery of Granulocyte-Macrophage Colony-Stimulating Factor and Interleukin 4 into Cd14+ Monocytes Generates Dendritic Cells in Vitro. Hum Gene Ther. 2004;15(8):733-48.

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