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GvHD, the most important cause of morbidity and mortality after allogeneic stem cell transplantation, depends primarily on the ability of a donor T-cell subset to react to immunogenic host Ag. Recently developed culture conditions and treatment strategies may bring us closer to the selective elimination of such alloreactive T cells, often considered the holy grail of transplantation. Among the various therapeutic modalities, photodynamic therapy (PDT) offers a biological and global approach to the eradication of unwanted allo-activated T cells by combining mitochondrial targeting, P-glycoprotein inhibition and reactive oxygen species production. Indeed, the high potency of PDT against malignant cells has been harnessed to exert selective and extensive elimination of alloreactive T-cell subsets mediating GvHD, while preserving resting T cells with the ability to reconstitute the immune system for GvL activity and prevent or suppress viruses and fungi. The present paper reviews the basis of the PDT strategy, and the methodology employed. In vitro and in vivo studies that formed the proof of principle as a basis for human studies to investigate the clinical potential of PDT in the context of GvHD will be presented together with insights into future clinical applications of this versatile treatment platform. [ABSTRACT FROM AUTHOR]

Background Priming with autologous tumor vaccine followed by ex vivo expansion of activated T cells is a feasible experimental strategy. This paper describes the application of this cellular therapy to treat patients with late-stage non-small-cell lung cancr (NSCLC). Methods Twenty-one patients with Stages III and IV NSCLC were treated. Tumor samples were obtained surgically (five patients) or by using a co-axial biopsy needle (16 patients). Each course of vaccination consisted of irradiated tumor cells, mixed with GM-CSF and injected intradermally on Day 1, followed by GM-CSF only on Days 2–5. The course was repeated 10–14 days later. Lymphocytes were collected 10–14 days after the second course and ex vivo expanded using IL-2 and anti-CD3 Ab. The expansion products were then re-infused into the patients. Results Twelve out of 16 biopsies resulted in optimal cell numbers for vaccine preparation. Nineteen out of 21 patients achieved a delayed type hypersensitivity (DTH) response after two courses of vaccination. In 18/21 patients, the ex vivo expansion products contained >1.6×10 10 cells. Subset analysis showed 77.0–97.2% T cells with a CD4:CD8 ratio of 0.65–4.0; natural killer cells were 2.0–18.6%. There were no significant toxicities. The median survival of all 21 patients was 18.6 months, with a 1-year survival of 51.6%. Conclusion Autologous tumor cell-vaccination may be combined with ex vivo expansion of lymphocytes as adoptive cellular immunotherapy for advanced NSCLC. Overall survival in this cohort of poor prognosis patients compared favorably with results reported in the literature. [ABSTRACT FROM AUTHOR]