The Science
Innovative Technology
Tat-MYC
Fusion protein that passively enters cells without the need for a surface receptor.
We transiently elevate MYC protein levels in treated cells for 3-5 days.
Recombinant protein eventually degrades
Tat-MYC and IL-2R pathway
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Tat-MYC enters cells in a passive manner, without the need to interact with a cell surface receptor.
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Tat-MYC localizes to the cell’s nucleus shortly after entry through the plasma membrane.
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The transcriptional regulatory activity of MYC leads to increased expression and function of Akt, among other gene products.
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Akt and MYC enter a positive feedback loop which promotes the proliferation and survival of the cell. The degradation of MYC naturally leads to the wind down of these activities.
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Genetic loss of function studies showed that MYC expression is critical for IL-2 dependent T cell proliferation and survival and could not be overcome by overexpression of a constitutively active form of Akt.
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Genetic gain of function studies showed that a surfeit of MYC can replace IL-2 dependent signaling for T cell proliferation and survival, or IL-4 in the case of B cells. In addition, MYC overexpression led to the increase in Akt and Bck-2 expression and activity in T cells.
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Tat-MYC fusion protein is able to mimic IL-2 in T cell functional assays.
Clinical
Current Clinical Use
RIB-001 is conditionally approved under a self-pay program in Japan by the Japanese Ministry of Health, Labor and Welfare for use in patients with cancer, chronic viral infections and healthy patients wanting to boost their immune function. RIB-001 is currently available in 3 clinics in Japan located in Tokyo and Sendai.
Upcoming Clinical Trial
Bedside use of RIX-001 will soon be tested for efficacy in a large patient population of Stage III/IV colorectal cancer patients who have exhausted standard of care in a clinical trial that will be regulated by the Israeli Ministry of Health and registered with the US FDA. The clinical trial will be carried out at the Davidoff Cancer Center in the Beilinson Medical Center in Petach Tikvah, Israel. The innovative element involved in this clinical trial will be the incorporation of the XynVivo system for extracorporeal cell processing contributed by our colleagues at Lupagen, Inc. This extracorporeal system will enable us to generate RIX-001 cells at point of care. This novel manufacturing approach will be key for allowing us to scale distribution and reduce cost in the long term.
Publications
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PLoS HSC paper
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PNAS anergy paper