TY  - JOUR
A1  - Wilhelm, Martin
A1  - Smetak, Manfred
A1  - Schaefer-Eckart, Kerstin
A1  - Kimmel, Brigitte
A1  - Birkmann, Josef
A1  - Einsele, Hermann
A1  - Kunzmann, Volker
T1  - Successful adoptive transfer and in vivo expansion of haploidentical γδ T cells
JF  - Journal of Translational Medicine
N2  - Background: The primary aim of this pilot study was to determine the feasibility and safety of an adoptive transfer and in vivo expansion of human haploidentical gamma delta T lymphocytes. 
Methods: Patients with advanced haematological malignancies who are not eligible for allogeneic transplantation received peripheral blood mononuclear cells from half-matched family donors. For that, a single unstimulated leukapheresis product was incubated with both the anti-CD4 and anti-CD8 antibodies conjugated to paramagnetic particles. The depletion procedure was performed on a fully automated CliniMACS (R) device according to the manufacturer's instructions. On average, patients received 2.17 x 10(6)/kg (range 0.9-3.48) γδ T cells with <1% CD4-or CD8-positive cells remaining in the product. All patients received prior lymphopenia-inducing chemotherapy (fludarabine 20-25 mg/m(2) day -6 until day -2 and cyclophosphamide 30-60 mg/kg day -6 and -5) and were treated with 4 mg zoledronate on day 0 and 1.0x10(6) IU/m(2) IL-2 on day +1 until day +6 for the induction of gamma delta T cell proliferation in vivo. 
Results: This resulted in a marked in vivo expansion of donor γδ T cells and, to a lower extent, natural killer cells and double-negative αβ T cells (mean 68-fold, eight-fold, and eight-fold, respectively). Proliferation peaked by around day +8 and donor cells persisted up to 28 days. Although refractory to all prior therapies, three out of four patients achieved a complete remission, which lasted for 8 months in a patient with plasma cell leukaemia. One patient died from an infection 6 weeks after treatment. 
Conclusion: This pilot study shows that adoptive transfer and in vivo expansion of haploidentical γδ T lymphocytes is feasible and suggests a potential role of these cells in the treatment of haematological diseases.
KW  - NK cells
KW  - in vivo cell expansion
KW  - haploidentical γδ T lymphocytes
KW  - adoptive transfer
KW  - CD4(+)
KW  - innate immunity
KW  - stimulation
KW  - acute myeloid-leukemia
KW  - immunotherapy
KW  - cancer
KW  - infusion
KW  - Interleukin-2
KW  - biophosphonate
Y1  - 2014
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-117290
VL  - 12
IS  - 45
ER  - 
TY  - JOUR
A1  - Metzenmacher, Martin
A1  - Váraljai, Renáta
A1  - Hegedüs, Balazs
A1  - Cima, Igor
A1  - Forster, Jan
A1  - Schramm, Alexander
A1  - Scheffler, Björn
A1  - Horn, Peter A.
A1  - Klein, Christoph A.
A1  - Szarvas, Tibor
A1  - Reis, Hennig
A1  - Bielefeld, Nicola
A1  - Roesch, Alexander
A1  - Aigner, Clemens
A1  - Kunzmann, Volker
A1  - Wiesweg, Marcel
A1  - Siveke, Jens T.
A1  - Schuler, Martin
A1  - Lueong, Smiths S.
T1  - Plasma Next Generation Sequencing and Droplet Digital-qPCR-Based Quantification of Circulating Cell-Free RNA for Noninvasive Early Detection of Cancer
JF  - Cancers
N2  - Early detection of cancer holds high promise for reducing cancer-related mortality. Detection of circulating tumor-specific nucleic acids holds promise, but sensitivity and specificity issues remain with current technology. We studied cell-free RNA (cfRNA) in patients with non-small cell lung cancer (NSCLC; n = 56 stage IV, n = 39 stages I-III), pancreatic cancer (PDAC, n = 20 stage III), malignant melanoma (MM, n = 12 stage III-IV), urothelial bladder cancer (UBC, n = 22 stage II and IV), and 65 healthy controls by means of next generation sequencing (NGS) and real-time droplet digital PCR (RT-ddPCR). We identified 192 overlapping upregulated transcripts in NSCLC and PDAC by NGS, more than 90% of which were noncoding. Previously reported transcripts (e.g., HOTAIRM1) were identified. Plasma cfRNA transcript levels of POU6F2-AS2 discriminated NSCLC from healthy donors (AUC = 0.82 and 0.76 for stages IV and I–III, respectively) and significantly associated (p = 0.017) with the established tumor marker Cyfra 21-1. cfRNA yield and POU6F2-AS transcript abundance discriminated PDAC patients from healthy donors (AUC = 1.0). POU6F2-AS2 transcript was significantly higher in MM (p = 0.044). In summary, our findings support further validation of cfRNA detection by RT-ddPCR as a biomarker for early detection of solid cancers.
KW  - liquid biopsy
KW  - cfRNA
KW  - cancer
KW  - ddPCR
KW  - NGS
KW  - POU6F2-AS2
KW  - early detection
Y1  - 2020
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-200553
SN  - 2072-6694
VL  - 12
IS  - 2
ER  -