Suicide gene
AssigneeBoard of Regents, The University of Texas System
InventorsKaty Rezvani, Elizabeth Shpall
Life of this patent
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Abstract
Embodiments of the disclosure encompass particular TNF-alpha mutants that are nonsecretable and membrane bound, thereby providing a target for inhibition in cells that express the mutants. In specific embodiments, the TNF-alpha mutants are utilized as a suicide gene in cells employed for adoptive cell therapy for an individual, wherein at a desired time the individual is provided one or more anti-TNF-alpha antibodies that bind the membrane bound TNF-alpha and elicit complement-dependent cytotoxicity for the cells. The TNF-alpha mutant can also be used as a way of tracking the transduced cells in vivo.
Claims47
A composition comprising a transduced cell comprising a nucleic acid that encodes one or more engineered nonsecretable tumor necrosis factor (TNF)-alpha mutant polypeptides and a nucleic acid that encodes one or more therapeutic gene products.
A method of inducing death for a transduced cell expressing an engineered nonsecretable TNF-alpha mutant polypeptide, comprising the step of providing an effective amount of at least one agent that binds the TNF-alpha mutant on the transduced cell.
A method of reducing the effects of cytokine release syndrome in an individual that has received and/or who is receiving cell therapy with cells that express a nonsecretable TNF-alpha mutant, comprising the step of providing an effective amount of one or more agents that bind the mutant to cause in the individual (a) elimination of at least some of the cells of the cell therapy;
- and (b) reduction in the level of soluble TNF-alpha.
A method of reducing the risk of toxicity of a cell therapy for an individual, comprising the step of modifying the cells of the cell therapy to express a nonsecretable TNF-alpha mutant.
A vector, comprising a sequence that encodes a nonsecretable TNF-alpha mutant and that encodes an engineered receptor.
As a composition of matter, a nucleic acid sequence comprising SEQ ID NO:15.
As a composition of matter, a nucleic acid sequence comprising SEQ ID NO:16.
Dependencies are inferred from the claim text.