Redirection to the bone marrow improves T cell persistence and antitumor functions.

A key predictor for the success of gene-modified T cell therapies for cancer is the persistence of transferred cells in the patient. The propensity of less differentiated memory T cells to expand and survive efficiently has therefore made them attractive candidates for clinical application. We hypothesized that redirecting T cells to specialized niches in the BM that support memory differentiation would confer increased therapeutic efficacy.

Genetic Regulation of Fate Decisions in Therapeutic T Cells to Enhance Tumor Protection and Memory Formation.

A key challenge in the field of T-cell immunotherapy for cancer is creating a suitable platform for promoting differentiation of effector cells while at the same time enabling self-renewal needed for long-term memory. Although transfer of less differentiated memory T cells increases efficacy through greater expansion and persistence in vivo, the capacity of such cells to sustain effector functions within immunosuppressive tumor microenvironments may still be limiting. We have therefore directly compared the impact of effector versus memory differentiation of therapeutic T cells in tumor-bearing mice by introducing molecular switches that regulate cell fate decisions via mTOR.

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.

CD8 T cell tolerance to a tumor-associated self-antigen is reversed by CD4 T cells engineered to express the same T cell receptor.

Ag receptors used for cancer immunotherapy are often directed against tumor-associated Ags also expressed in normal tissues. Targeting of such Ags can result in unwanted autoimmune attack of normal tissues or induction of tolerance in therapeutic T cells. We used a murine model to study the phenotype and function of T cells redirected against the murine double minute protein 2 (MDM2), a tumor-associated Ag that shows low expression in many normal tissues.

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.

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.

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.

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.