Adoptive cell transfer

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The adoptive cell transfer refers to the transfer of cells into an organism .

properties

Adoptive T cell transfer

By treating cells ex vivo with a vector , immunogen, or drug , effects can be achieved that are not always achieved in vivo . For example, an active ingredient used for treatment can be broken down or excreted prematurely in the organism (e.g. by the liver ) or the active ingredient only develops toxicity in the body . Cell transfer consists of the removal of cells (whether autologous or non-autologous), their treatment ex vivo and their transfer, usually by injection or infusion , into an organism. Through the transfer or, in the case of autologous cells, through the return transfer, the organism receives cells with new functions, which is where the term adoptive comes from.

In immunology , mostly autologous immune cells ( PBMC , mainly T-lymphocytes , cytokine-induced killer cells and dendritic cells ) are isolated by density gradient centrifugation and then treated in cell culture . Sometimes there is a cell depletion of undesired cell types. In the case of vaccines , this treatment of the cells can be stimulating (e.g. with interleukin-2 , GM-CSF , IL-12 , IL-21 ) or tolerogenic in the case of hyposensitization (e.g. with anti- CD3 receptor antibodies such as Muromonab-CD3 , otelixizumab , Teplizumab and visilizumab ).

Applications

The adoptive cell transfer is used, among other things, in gene therapy , in stem cell therapy or in immunotherapy . Sipuleucel-T is an approved adoptive cell transfer.

In the context of cancer immunotherapy , immune cells are sensitized ex vivo against tumor cells . In a clinical study with an adoptive cell transfer of transgenic T cells, a remission rate of 88% was achieved in patients with B cell lymphomas .

Inoculation with tumor antigen-loaded dendritic cells is also the subject of current research and clinical studies. In this case, autologous dendritic cells are loaded ex vivo with antigens which either come directly from the patient's individual tumor or which are used for standardized treatment (MelanA, survivin). The loading of the dendritic cells can take place inter alia by means of RNA transfection, DNA transfer or incubation with tumor lysate. Furthermore, tumor cells are transfected with genes of cytokines which, after injection, preferentially bind to other tumor cells of the same type and there cause or intensify the immune reaction via the cytokine secreted by them .

Another method that can be counted as adoptive cell transfer and is in the experimental stage with animals was presented for the first time in 2015. Immune system cells of the affected animal were placed on a silicon grid with an extremely fine structure. These cells were activated in vitro (outside the organism) with attenuated pathogens. The grid was then implanted on the animal and could remain there for a few months. The method has not yet been tested on humans.

Individual evidence

  1. ↑ C. Hontscha, Y. Borck, H. Zhou, D. Messmer, IG Schmidt-Wolf: Clinical trials on CIK cells: first report of the international registry on CIK cells (IRCC). In: Journal of Cancer Research and Clinical Oncology . Volume 137, Number 2, February 2011, pp. 305-310, doi: 10.1007 / s00432-010-0887-7 . PMID 20407789 .
  2. ^ C. Berger, CJ Turtle, MC Jensen, SR Riddell: Adoptive transfer of virus-specific and tumor-specific T cell immunity. In: Current Opinion in Immunology . Volume 21, Number 2, April 2009, pp. 224-232, doi: 10.1016 / j.coi.2009.02.010 . PMID 19304470 . PMC 2720155 (free full text).
  3. ↑ G. Vassalli: Dendritic Cell-Based Approaches for Therapeutic Immune Regulation in Solid-Organ Transplantation. In: Journal of transplantation. Volume 2013, 2013, p. 761429, doi: 10.1155 / 2013/761429 . PMID 24307940 . PMC 3824554 (free full text).
  4. ↑ Gattinoni L, Powell DJ, Rosenberg SA, Restifo NP: Adoptive immunotherapy for cancer: building on success . In: Nature Reviews Immunology . 6, No. 5, May 2006, pp. 383-93. doi : 10.1038 / nri1842 . PMID 16622476 . PMC 1473162 (free full text).
  5. ↑ June CH: Adoptive T cell therapy for cancer in the clinic . In: The Journal of Clinical Investigation . 117, No. 6, June 2007, pp. 1466-76. doi : 10.1172 / JCI32446 . PMID 17549249 . PMC 1878537 (free full text).
  6. ^ Schmitt ™, Ragnarsson GB, Greenberg PD: T Cell Receptor Gene Therapy for Cancer . In: Human Gene Therapy . 20, No. 11, October 2009, pp. 1240-8. doi : 10.1089 / hum.2009.146 . PMID 19702439 . PMC 2829456 (free full text).
  7. ^ Riley JL, June CH, Blazar BR: Human T Regulatory Cells as Therapeutic Agents: Take a Billion or So of These and Call Me in the Morning . In: Immunity . 30, No. 5, May 2009, pp. 656-65. doi : 10.1016 / j.immuni.2009.04.006 . PMID 19464988 . PMC 2742482 (free full text).
  8. ↑ M. Michael, A. Shimoni, A. Nagler: Regulatory T cells in allogeneic stem cell transplantation. In: Clinical & developmental immunology. Volume 2013, 2013, p. 608951, doi: 10.1155 / 2013/608951 . PMID 23737813 . PMC 3662184 (free full text).
  9. ↑ Johnson LA, Morgan RA, Dudley ME, et al. : Gene therapy with human and mouse T-cell receptors mediates cancer regression and targets normal tissues expressing cognate antigen . In: Blood . 114, No. 3, July 2009, pp. 535-46. doi : 10.1182 / blood-2009-03-211714 . PMID 19451549 . PMC 2929689 (free full text).
  10. ↑ Morgan RA, Dudley ME, Wunderlich JR, et al. : Cancer Regression in Patients After Transfer of Genetically Engineered Lymphocytes . In: Science . 314, No. 5796, October 2006, pp. 126-9. doi : 10.1126 / science.1129003 . PMID 16946036 . PMC 2267026 (free full text).
  11. ↑ Kalos M, Levine BL, Porter DL, et al. : T Cells with Chimeric Antigen Receptors Have Potent Antitumor Effects and Can Establish Memory in Patients with Advanced Leukemia . In: Science Translational Medicine . 3, No. 95, August 2011, p. 95ra73. doi : 10.1126 / scitranslmed.3002842 . PMID 21832238 .
  12. ↑ A. Kunert, T. Straetemans, C. Govers, C. Lamers, R. Mathijssen, p Sleijfer, R. debits: TCR Engineered T Cells Meet New Challenges to Treat Solid tumor: Choice of antigen, T cell fitness, and Sensitization of Tumor Milieu. In: Frontiers in immunology. Volume 4, 2013, p. 363, doi: 10.3389 / fimmu.2013.00363 . PMID 24265631 . PMC 3821161 (free full text).
  13. ↑ Besser MJ, Shapira-Frommer R, Treves AJ, et al. (May 2010). "Clinical responses in a phase II study using adoptive transfer of short-term cultured tumor infiltration lymphocytes in metastatic melanoma patients" Clin. Cancer Res 16 (9) 2646-2655. doi: 10.1158 / 1078-0432.CCR-10-0041 PMID 20406835
  14. ↑ Dudley ME, Wunderlich JR, Robbins PF, et al. : Cancer Regression and Autoimmunity in Patients After Clonal Repopulation with Antitumor Lymphocytes . In: Science . 298, No. 5594, October 2002, pp. 850-4. doi : 10.1126 / science.1076514 . PMID 12242449 . PMC 1764179 (free full text).
  15. ↑ Dudley ME, Wunderlich JR, Yang JC, et al. : Adoptive Cell Transfer Therapy Following Non-Myeloablative but Lymphodepleting Chemotherapy for the Treatment of Patients With Refractory Metastatic Melanoma . In: Journal of Clinical Oncology . 23, No. 10, April 2005, pp. 2346-57. doi : 10.1200 / JCO.2005.00.240 . PMID 15800326 . PMC 1475951 (free full text).
  16. ↑ ML Davila, I. Riviere, X. Wang, S. Bartido, J. Park, K. Curran, SS Chung, J. Stefanski, O. Borquez-Ojeda, M. Olszewska, J. Qu, T. Wasielewska, Q He, M. Fink, H. Shinglot, M. Youssif, M. Satter, Y. Wang, J. Hosey, H. Quintanilla, E. Halton, Y. Bernal, DC Bouhassira, ME Arcila, M. Gonen, GJ Roboz, P. Maslak, D. Douer, MG Frattini, S. Giralt, M. Sadelain , R. Brentjens: Efficacy and toxicity management of 19-28z CAR T cell therapy in B cell acute lymphoblastic leukemia. In: Science Translational Medicine . Volume 6, number 224, February 2014, p. 224ra25, doi: 10.1126 / scitranslmed.3008226 . PMID 24553386 .
  17. ↑ Sébastien Anguille, Evelien L Smits, Eva Lion, Viggo F van Tendeloo, Zvi N Berneman: Clinical use of dendritic cells for cancer therapy. In: The Lancet Oncology. 15, 2014, p. E257, doi: 10.1016 / S1470-2045 (13) 70585-0 .
  18. ↑ Eleonora Dondossola, Andrey S. Dobroff, Serena Marchiò, Marina Cardó-Vila, Hitomi Hosoya, Steven K. Libutti, Angelo Corti, Richard L. Sidman, Wadih Arap, Pasqualini Renata: Self-targeting of TNF-releasing cancer cells in preclinical models of primary and metastatic tumors. In: Proceedings of the National Academy of Sciences. , S. 201525697, doi: 10.1073 / pnas.1525697113 .
  19. ↑ Implantable vaccine development using in vitro antigen-pulsed macrophages absorbed on laser micro-structured Si scaffolds . Retrieved April 2, 2020.