Safety of Repeated Administration of Xenogeneic Human Apoptotic State (Allocetra-OTS) in Sprague Dawley Rats.

Apoptotic cells possess immunomodulatory effects that can be utilized to treat imbalanced immune conditions. Information on the preclinical safety of such treatment is sparse. In this study, the safety of apoptotic cells (Allocetra-OTS) was assessed in a GLP toxicological study on Sprague Dawley rats.

Novel immunotherapy for malignant melanoma with a monoclonal antibody that blocks CEACAM1 homophilic interactions.

CEACAM1 (biliary glycoprotein-1, CD66a) was reported as a strong clinical predictor of poor prognosis in melanoma. We have previously identified CEACAM1 as a tumor escape mechanism from cytotoxic lymphocytes. Here, we present substantial evidence in vitro and in vivo that blocking of CEACAM1 function with a novel monoclonal antibody (MRG1) is a promising strategy for cancer immunotherapy.

Regulation of cancer aggressive features in melanoma cells by microRNAs.

MicroRNAs (miRNAs) are small non-coding RNAs with regulatory roles, which are involved in a broad spectrum of physiological and pathological processes, including cancer. A common strategy for identification of miRNAs involved in cell transformation is to compare malignant cells to normal cells. Here we focus on identification of miRNAs that regulate the aggressive phenotype of melanoma cells.

Establishment and large-scale expansion of minimally cultured "young" tumor infiltrating lymphocytes for adoptive transfer therapy.

Treatment of metastatic melanoma patients with adoptively transferred tumor infiltrating lymphocytes (TIL) has developed into an effective therapy. Various studies reported objective responses of 50% and more. The use of unselected, minimally cultured, bulk TIL (Young-TIL) has simplified the TIL production process and may therefore, allow the accessibility of this approach to cancer centers worldwide.

Focus on adoptive T cell transfer trials in melanoma.

Adoptive Cell Transfer (ACT) of Tumor-Infiltrating Lymphocytes (TIL) in combination with lymphodepletion has proven to be an effective treatment for metastatic melanoma patients, with an objective response rate in 50%-70% of the patients. It is based on the ex vivo expansion and activation of tumor-specific T lymphocytes extracted from the tumor and their administration back to the patient. Various TIL-ACT trials, which differ in their TIL generation procedures and patient preconditioning, have been reported.

Clinical responses in a phase II study using adoptive transfer of short-term cultured tumor infiltration lymphocytes in metastatic melanoma patients.

Purpose: Adoptive cell therapy with autologous tumor-infiltrating lymphocytes (TIL) has shown promising results in metastatic melanoma patients. Although objective response rates of over 50% have been reported, disadvantages of this approach are the labor-intensive TIL production and a very high drop-out rate of enrolled patients, limiting its widespread applicability. Previous studies showed a clear correlation between short TIL culture periods and clinical response.

Adrenal 20alpha-hydroxysteroid dehydrogenase in the mouse catabolizes progesterone and 11-deoxycorticosterone and is restricted to the X-zone.

The enzyme 20alpha-hydroxysteroid dehydrogenase (20alpha-HSD) is a progesterone-catabolizing enzyme that is highly expressed in mouse ovaries and adrenals. Although the functional significance of ovarian 20alpha-HSD for the induction of parturition has been defined, regulation and distribution of 20alpha-HSD in the adrenal gland has not been determined. We demonstrate that the expression of adrenal 20alpha-HSD is restricted to the X-zone, a transient zone between the adrenal cortex and the medulla of yet unknown function.