Prospective multicenter clinical trial of immunosuppressive drug withdrawal in stable adult liver transplant recipients.

Unlabelled: Lifelong immunosuppression increases morbidity and mortality in liver transplantation. Discontinuation of immunosuppressive drugs could lessen this burden, but the safety, applicability, and clinical outcomes of this strategy need to be carefully defined. We enrolled 102 stable liver recipients at least 3 years after transplantation in a single-arm multicenter immunosuppression withdrawal trial.

Modulation of anti-tumor necrosis factor alpha (TNF-α) antibody secretion in mice immunized with TNF-α kinoid.

Tumor necrosis factor alpha (TNF-α) blockade is an effective treatment for patients with TNF-α-dependent chronic inflammatory diseases, such as rheumatoid arthritis, Crohn's disease, and psoriasis. TNF-α kinoid, a heterocomplex of human TNF-α and keyhole limpet hemocyanin (KLH) (TNF-K), is an active immunotherapy targeting TNF-α. Since the TNF-K approach is an active immunization, and patients receiving this therapy also receive immunosuppressant treatment, we evaluated the effect of some immunosuppressive drugs on the generation of anti-TNF-α antibodies produced during TNF-K treatment.

Market access challenges in the EU for high medical value diagnostic tests.

The clinical utility and medico-economic value of several personalized diagnostic tests has been well described in the literature. Development of such tests, including generation of the necessary supportive clinical validation data, is a complex and expensive endeavor. In general, sponsors of such tests lack sufficient clarity on appropriate reimbursement and regulatory pathways to provide the clear development framework necessary to incentivize the required level of investment.

IFNalpha kinoid vaccine-induced neutralizing antibodies prevent clinical manifestations in a lupus flare murine model.

A major involvement of IFNalpha in the etiopathogenesis of systemic lupus erythematosus has been suggested by clinical observations, including the increase of serum levels of this cytokine in patients with active disease. Supporting this hypothesis, we have shown that expression of IFNalpha from a recombinant adenovirus (IFNalpha Adv) precipitates lupus manifestations in genetically susceptible New Zealand Black (NZB) x New Zealand White (NZW)F(1) mice (NZB/W) but not in BALB/c mice. In the present investigation, we have prepared an IFNalpha immunogen, termed IFNalpha kinoid, which, appropriately adjuvanted, induces transient neutralizing antibodies (Abs) but no cellular immune response to the cytokine and without apparent side effects.

Control of allergic reactions in mice by an active anti-murine IL-4 immunization.

Pathogenesis of allergic inflammatory disorders is characterized by allergen-induced IgE stimulated by Th2 cytokines including mainly IL-4 overproduction. To counteract IL-4 effects in sensitized-BALB/c mice, we prepared an IL-4 derivative immunogen, made of KLH and murine IL-4 heterocomplex, termed mIL-4 kinoid. Murine IL-4 kinoid immunized mice produced high titer of anti-IL-4 neutralizing Abs.

VEGF kinoid vaccine, a therapeutic approach against tumor angiogenesis and metastases.

Tumor growth depends on blood supply, requiring the development of new vessels, and vascular endothelial growth factor (VEGF) plays a central role in neoangiogenic processes. For this reason, VEGF represents a target for the development of new therapeutic antiangiogenic molecules. Clinical trials using anti-VEGF mAbs such as bevacizumab have validated the efficacy of this therapeutic approach but have also revealed adverse effects.