Automated Expansion of Primary Human T Cells in Scalable and Cell-Friendly Hydrogel Microtubes for Adoptive Immunotherapy.

Adoptive immunotherapy is a highly effective strategy for treating many human cancers, such as melanoma, cervical cancer, lymphoma, and leukemia. Here, a novel cell culture technology is reported for expanding primary human T cells for adoptive immunotherapy. T cells are suspended and cultured in microscale alginate hydrogel tubes (AlgTubes) that are suspended in the cell culture medium in a culture vessel. The hydrogel tubes protect cells from hydrodynamic stresses and confine the cell mass less than 400 µm (in radial diameter) to ensure efficient mass transport, creating a cell-friendly microenvironment for growing T cells. This system is simple, scalable, highly efficient, defined, cost-effective, and compatible with current good manufacturing practices. Under optimized culture conditions, the AlgTubes enable culturing T cells with high cell viability, low DNA damage, high growth rate (≈320-fold expansion over 14 days), high purity (≈98% CD3+), and high yield (≈3.2 × 108 cells mL-1 hydrogel). All offer considerable advantages compared to current T cell culturing approaches. This new culture technology can significantly reduce the culture volume, time, and cost, while increasing the production.

Scalable Culturing of Primary Human Glioblastoma Tumor-Initiating Cells with a Cell-Friendly Culture System.

Glioblastoma is the most aggressive and deadly brain cancer. There is growing interest to develop drugs that specifically target to glioblastoma tumor-initiating cells (TICs). However, the cost-effective production of large numbers of high quality glioblastoma TICs for drug discovery with current cell culturing technologies remains very challenging. Here, we report a new method that cultures glioblastoma TICs in microscale alginate hydrogel tubes (or AlgTubes). The AlgTubes allowed long-term culturing (~50 days, 10 passages) of glioblastoma TICs with high growth rate (~700-fold expansion/14 days), high cell viability and high volumetric yield (~3.0 × 108 cells/mL) without losing the stem cell properties, all offered large advancements over current culturing methods. This method can be applied for the scalable production of glioblastoma TICs at affordable cost for drug discovery.

Dual and triple therapy to prevent mother-to-child transmission of HIV in a resource-limited setting - lessons from a South African programme.

OBJECTIVE: To determine outcomes of pregnant women and their infants at McCord Hospital in Durban, South Africa, where dual and triple therapy to reduce HIV vertical transmission have been used since 2004 despite national guidelines recommending simpler regimens. METHOD: We retrospectively examined records of all pregnant women attending McCord Hospital for their first antenatal visit between 1 March 2004 and 28 February 2007. Uptake of HIV testing and HIV prevalence were determined, and clinical, immunological and virological outcomes of HIV-positive women and their infants, followed through to 6 months after delivery, were described. RESULTS: The antenatal clinic was attended by 5 303 women; 4 891 (92%) had an HIV test, and 703 (14%) were HIV positive. The HIV-positive women were subsequently followed up: 653 (93%) received antiretroviral therapy or prophylaxis, including 424 (60%) who received triple therapy. Of the 699 live babies delivered, 661 (94%) received prophylaxis. At 6 weeks 571 babies (82%) were brought back for HIV testing; 16 (2.8%) were HIV positive. After 6 months, only 150 women (21%) were receiving follow-up care at the adult HIV clinic. CONCLUSION: Where a tailored approach to prevention of mother-to-child transmission (PMTCT) is used, which attempts to maximise available technology and resources, good short-term transmission outcomes can be achieved. However, longer-term follow-up of mothers' and babies' health presents a challenge. Successful strategies to link women to ongoing care are crucial to sustain the gains of PMTCT programmes.