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Nucleic acid encoding a lectin-derived progenitor cell preservation factor
| Details |
Inventors: Colucci, M. Gabriella; Chrispeels, Maarten J.; Moore, Jeffrey G.;
Assignee: ImClone Systems Incorporated (New York, NY)
Primary Examiner: Saunders; David
Assistant Examiner: Tung; Mary Beth
Attorney, Agent or Firm: Hale and Dorr LLP
The invention relates to an isolated nucleic acid molecule that encodes a protein that is effective to preserve progenitor cells, such as hematopoietic progenitor cells. The nucleic acid comprises a sequence defined by SEQ ID NO:1, a homolog thereof, or a fragment thereof. The encoded protein has an amino acid sequence that comprises a sequence defined by SEQ ID NO:2, a homolog thereof, or a fragment thereof that contains an amino acid sequence TNNVLQVT. Methods of using the encoded protein for preserving progenitor cells in vitro, ex vivo, and in vivo are also described. The invention, therefore, include methods such as myeloablation therapies for cancer treatment wherein myeloid reconstitution is facilitated by means of the specified protein. Other therapeutic utilities are also enabled through the invention, for example, expanding progenitor cell populations ex vivo to increase chances of engraftation, improving conditions for transporting and storing progenitor cells, and facilitating gene therapy to treat and cure a broad range of life-threatening hematologic diseases. |
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DETAILED DESCRIPTION It has now been discovered that these and other objectives can be achieved by the present invention, which provides an isolated nucleic acid comprising a nucleotide sequence as defined by SEQ ID NO:1, a homolog thereof, or a unique fragment thereof that encodes an amino acid sequence TNNVLQVT (SEQ ID NO.
:24).
The isolated nucleic acid preferably encodes a mannose/glucose-specific legume lectin, and is more preferably isolated from a legume of the tribe Phaseoleae.
Most preferably, the protein is encoded by a nucleic acid that is isolated from red kidney beans, white kidney beans, hyacinth beans, or black-eyed peas.
The isolated nucleic acid of the invention preferably comprises a nucleotide sequence as defined by SEQ ID NO:1 or a unique fragment thereof.
Also, the protein encoded by the nucleic acid of the invention is capable of preserving progenitor cells that are at least unipotent progenitor cells, but the protein can be used to preserve pluripotent progenitor cells, as well as totipotent progenitor cells.
In a preferred case, the protein can preserve hematopoietic progenitor cells, but progenitor cells from other tissues can also be preserved, including nerve, muscle, skin, gut, bone, kidney, liver, pancreas, or thymus progenitor cells.
The progenitor cells capable of preservation according to the invention may express the CD34 antigen.
More preferably, the progenitor cells express both CD34 and the FLK2/FLT3 receptor.
Still more preferably, the progenitor cells express the FLK2/FLT3 receptor but do not express CD34.
The protein can also be used to preserve cells that have been modified to express FLK2/FLT3 receptors on their surface.
Thus, the invention provides a protein that has significant binding affinity for FLK2/FLT3 receptor on the cells, wherein binding of the protein with the FLK2/FLT3 receptor mediates the inhibition of differentiation of the cells.
The invention further provides a method for preserving progenitor cells, comprising contacting progenitor cells with a protein encoded by an isolated nucleic acid comprising a nucleotide sequence defined by SEQ ID NO:1, a homolog thereof, or a fragment thereof that encodes an amino acid sequence TNNVLQVT, in an amount sufficient to preserve the progenitor cells
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