Overcoming Target Driven Fratricide for T Cell Therapy.

Chimeric Antigen Receptor (CAR) T cells expressing the fusion of the NKG2D protein with CD3ζ (NKG2D-CAR T Cells) acquire a specificity for stress-induced ligands expressed on hematological and solid cancers. However, these stress ligands are also transiently expressed by activated T cells implying that NKG2D-based T cells may undergo self-killing (fratricide) during cell manufacturing or during the freeze thaw cycle prior to infusion in patients. To avoid target-driven fratricide and enable the production of NKG2D-CAR T cells for clinical application, two distinct approaches were investigated.

Cardiopoietic index predicts heart repair fitness of patient-derived stem cells.

Background: Stem cell therapy shows promise for regeneration in heart disease, yet interpatient variability challenges implementation into practice.

Aim: To establish a biomarker profile, predictive of reparative potential in patient-derived progenitors, human mesenchymal stem cells were isolated from patients undergoing coronary artery bypass grafting.

Materials & Methods: Stem cell delivery postinfarction translated into divergent benefit, distinguishing reparative from nonreparative populations.

Guidelines for translational research in heart failure.

Heart failure (HF) remains a major cause of death and hospitalization worldwide. Despite medical advances, the prognosis of HF remains poor and new therapeutic approaches are urgently needed. The development of new therapies for HF is hindered by inappropriate or incomplete preclinical studies.

Toward cell therapy using placenta-derived cells: disease mechanisms, cell biology, preclinical studies, and regulatory aspects at the round table.

Among the many cell types that may prove useful to regenerative medicine, mounting evidence suggests that human term placenta-derived cells will join the list of significant contributors. In making new cell therapy-based strategies a clinical reality, it is fundamental that no a priori claims are made regarding which cell source is preferable for a particular therapeutic application. Rather, ongoing comparisons of the potentiality and characteristics of cells from different sources should be made to promote constant improvement in cell therapies, and such comparisons will likely show that individually tailored cells can address disease-specific clinical needs.

Efficacy and safety of the freeze-dried cultured human keratinocyte lysate, LyphoDerm 0.9%, in the treatment of hard-to-heal venous leg ulcers.

LyphoDerm (XCELLentis, Belgium) is an end-sterilized, freeze-dried lysate from cultured allogeneic epidermal keratinocytes, formulated into a hydrophilic gel. Its efficacy and safety were evaluated, in combination with standard care (hydrocolloid dressing and compression therapy), in 194 patients suffering from hard-to-heal (lasting more than 6 weeks and not responding to conventional therapy) venous leg ulcers. Two control groups received standard care, with or without vehicle, respectively.

Use of in Vitro Correlates for Selection of Candidate Immunosuppressive Antibodies Prior to a Primate Transplant Model.

The selection of possible candidate immunosuppressive antibodies to prevent graft rejection is performed in vitro. Additionally, due to the species specificity of these monoclonal antibodies (MABs), pre-clinical studies in non-human primates are necessary. If a positive correlation between the in vitro and in vivo findings would exist, these tests can act as a pre-screening before new reagents are tested in vivo.

Neuronal and mesodermal differentiation of P19 embryonal carcinoma cells is characterized by expression of specific marker genes and modulated by activin and fibroblast growth factors.

We have used the P19 embryonal carcinoma (EC) aggregation system as a model for early mouse development to study induction and modulation of mesodermal and neuronal differentiation. By studying the expression of marker genes for differentiated cells in this model we have shown that there is a good correlation between the differentiation direction induced in P19 EC aggregates and the expression of these genes. Expression of the neuronal gene midkine is exclusively upregulated when P19 EC cells are induced to form neurons while expression of early mesodermal genes such as Brachyury T, evx-1, goosecoid and nodal is elevated after induction to the mesodermal pathway.