Glick at the University of Michigan, is to develop orally available small molecules that exploit bioenergetic abnormalities in pathologically activated lymphocytes
and result in the selective silencing of these cells.
announced today results from a preclinical study for MDX-1401, a second-generation non-fucosylated version of MDX-060 that targets CD30, a marker for activated lymphocytes
that is present on the malignant cells of Hodgkin's lymphoma (HL) as well as other CD30-expressing cancers.
In the laboratory, a Giemsa stain of a smear prepared from the patient's blood showed activated lymphocytes
During this process a regulatory protein called cFLIP is produced, blocking apoptosis, or programmed cell death, in the activated lymphocytes
The possible immunopathologic mechanism of HLH might be excessive production of Th1 cytokines, such as gamma-interferon, tumor necrosis factor-alpha, interleukin-1, or interleukin-6, from activated lymphocytes
or monocytes (1,2).
The study, presented this week at the Midwinter Conference of Immunologists, represents a novel approach to specific immunotherapy by clonally deleting activated lymphocytes
responding to transplanted tissue.
MDX-1106/ONO-4538 is a novel fully human antibody designed to target and inhibit the function of PD-1 (programmed cell death 1), a receptor expressed on the surface of activated lymphocytes
(T-cells) that is involved in the system of negative regulation for the suppression of activated lymphocytes
On normal cells, CD30 expression is limited to a subset of activated lymphocytes
, making it an attractive target for antibody-based therapeutics.
MDX-060 is a fully human antibody that targets CD30, a marker found on activated lymphocytes
that is present on malignant cells of Hodgkin's disease (HD) as well as other CD30-expressing cancers.
Preclinical data for an anti-CD70 antibody in development by Medarex -- "Functional blocking and targeted depletion of activated lymphocytes
by fucosylated and non-fucosylated fully human anti-CD70 IgG1" (Presentation #1984, T-cell Biology and Targets in Autoimmune Disease Session) - Poster presentation scheduled for Saturday, November 10, 2007 at 8:00 A.
PD-1 (programmed cell death 1) is one of the receptors expressed on the surface of activated lymphocytes
(T-cells) and is involved in the system of negative regulation for the suppression of activated lymphocytes