T cell tuning for tumour therapy: Enhancing effector function and memory potential of therapeutic T cells.

The genetic engineering of T cells can lead to enhanced immune-mediated tumour destruction and harbors a great potential for the treatment of cancer. Recent efforts have centered on the design of receptors to re-direct the specificity of T cells towards tumour antigens by means of viral gene transfer. This strategy has shown great success in a number of phase one clinical trials. However, there are still challenges to overcome. On the one hand, T cell function can be further improved to optimize the therapeutic outcome. On the other hand, so called safety switches are required to deal with possible on and off target toxicities. In this review, we will give a brief summary of the success and risks of T cell gene therapy before discussing in detail current strategies to enhance effector function, persistence and safety of adoptively transferred T cells.

Outpatient follicle monitoring: a plea for standardization in ultrasound based follicle monitoring and data transfer.

BACKGROUND: The complexity of assisted reproductive technology (ART) increased during the last decades. New scientific and medical findings as well as the statutory requirements for improving the safety and the outcome of ART were the main impetus for its development. While therapy planning is done and ART is used by the IVF centers, the medical support and monitoring of patients is conducted by referring gynecologists. Reported follicle measurements by the gynecologist allow the adoption of the therapy plan. Most notably, the crucial aspect is processing and interpretation of ultrasound scan (US). The results of the received US, the transfer of data between IVF center(s) and referred physician(s) as well as the subjective interpretation often culminate in interpretation and logistical problems. This might increase the error probability with considerable detriments for the patients and ART outcome. METHODS: The follicle monitoring was performed using Voluson I ultrasound system combined with SonoAVC(®) software. Results were communicated via DICOM language to DynaMed(®) software, a medical program for managing an IVF center with seamless integration of all processes needed for an accurate and precise workflow. RESULTS: In this study, no loss of data was detected. All data were integrated by DynaMed(®) software and were recallable in a fast and easy manner. CONCLUSION: The broad usage of Voluson I ultrasound SonoAVC(®) software and communication of the results via Picture Archiving and Communication System (PACS) server between the IVF center and local gynecologist would provide more assistance for the patients and consequently the ART outcomes can be improved.

Dopamine agonist bromocriptine for the prevention of ovarian hyperstimulation syndrome.

The aim of this retrospective study is to investigate the frequency and severity of ovarian hyperstimulation syndrome and the pregnancy rate in a patient collective at risk who received bromocriptine treatment.

The rationale behind collecting umbilical cord blood.

Umbilical cord blood (UCB) is an increasingly important and rich source of stem cells. These cells can be used for the treatment of many diseases, including cancers and immune and genetic disorders. For patients for whom no suitable related donor is available, this source of hematopoietic stem cells offers substantial advantages, notably the relative ease of procurement, the absence of risk to the donor, the small likelihood of transmitting clinically important infections, the low risk of severe graft-versus-host disease (GVHD) and the rapid availability of placental blood for transplantation centers. Even though almost 80 diseases are treatable with cord blood stem cells, 97 percent of cord blood is still disposed of after birth and lost for patients in need! To improve availability of stem cells to a broader community, efforts should be undertaken to collect cord blood and expectant parents should be properly informed of their options with regard to cord blood banking.

Improved monitoring of ovarian stimulation using 3D transvaginal ultrasound plus automated volume count.

Two-dimensional transvaginal ultrasound (2D) is typically performed to monitor follicle growth in IVF and to determine the optimal time for administering human chorionic gonadotrophin. However, 2D only provides an approximation of the real volume of follicles and therefore cannot be used to guarantee standards for follicular measurement. The automated measurement of follicular size in three dimensions (3D) using a software programme that identifies and quantifies hypoechoic regions within a 3D dataset might provide an objective, fast, valid and reliable standard for such measurements. A prospective controlled study (group I: 20 patients, 2D; group II: 20 patients, 3D) investigated how the criteria for triggering oocyte maturation that are normally used in 2D compare to the new and more accurate method of measuring follicles using 3D-based automated volume count. Significantly more oocytes were fertilized (group 1: 7.1 +/- 4.5, group 2: 11.5 +/- 6.4; P < 0.03) when using 3D technology and automated volume count. The study assumes that the automated volume count more closely mirrors the biological reality, which means that it can also be used to guarantee the quality standards established by the European Union directive on tissues and cells (2004/23/EC). This new technology therefore holds great promise of becoming the new standard for monitoring follicular growth in IVF.

Non-informative results and monosomies in PGD: the importance of a third round of re-hybridization.

The incidence of non-informative results after fluorescence in-situ hybridization (FISH) was analysed in preimplantation genetic diagnosis (PGD). FISH was performed on seven chromosomes (13, 16, 18, 21, 22, X, and Y) in two rounds of hybridization (one biopsied blastomere per day 3 embryo). A third round with telomeric probes was performed in order to analyse the chromosome(s) in question. A total of 702 embryos out of a total of 719 embryos from 95 cycles were analysed. The remaining 17 embryos were anucleated and/or had poor quality and could not be diagnosed. After FISH analysis, 52.7% of blastomeres were found to be abnormal, 27.1% euploid, and 20.2% had non-informative results. Abnormalities considered as non-informative included 'monosomy in question' (46.5%), 'trisomy in question' (40.2%), compound aneuploidy (8.5%), and 'no result' (4.9%) for a tested chromosome. Following re-hybridization with telomeric probes, euploidy was found in 42.4% of 'monosomies in question,' in 82.4% of 'trisomies in question,' in 16.7% of compound aneuploidies, and in 71.4% of 'no results' for a tested chromosome. Only 4.2% of non-informative results could not be rescued. This study clearly demonstrates the importance of re-hybridizing non-informative results and monosomies using a third round of hybridization with telomeric probes for chromosome(s) in question.