摘要:
The present invention is directed to an isolated polynucleotide sequence encoding a chimeric TNFalpha, comprising a first nucleotide sequence encoding a domain or subdomain of a tumor necrosis factor ligand other than TNFalpha, wherein the encoded domain or subdomain replaces a cleavage site of native TNFalpha, and a second nucleotide sequence encoding a domain or subdomain of native TNFalpha that binds to a TNFalpha receptor. The encoded chimeric TNFalpha is significantly less susceptible to cleavage from the cellular surface and, as a result can increase the concentration of a ligand capable of binding to a TNFalpha receptor on the surface of a cell. The chimeric TNFalpha is therefore useful in methods for inducing apoptosis of a cell expressing a TNFalpha receptor, inducing activation of an immune system cell and treating neoplastic cells, by introducing into the cell of interest an isolated polynucleotide sequence encoding a chimeric TNFalpha that is expressed on the surface of the cell.
摘要:
Therapeutic antibodies having binding specificity for ROR-1 expressed on cancer cells (particularly leukemic and lymphomic cells) and pharmaceutical compositions containing one or more such antibodies for use in treating cancer. Methods for diagnosing such cancers through in vitro detection of binding to ROR-1 protein expressed on putative cancer cells are also provided.
摘要:
Therapeutic antibodies having binding specificity for ROR-1 expressed on cancer cells (particularly leukemic and lymphomic cells) and pharmaceutical compositions containing one or more such antibodies for use in treating cancer. Methods for diagnosing such cancers through in vitro detection of binding to ROR-1 protein expressed on putative cancer cells are also provided.
摘要:
What is provided are compositions comprising a purified, isolated antibody directed against ROR1, wherein the antibody binds ROR1 with moderate to high affinity. In addition, methods are provided for detecting and isolating an amount of ROR1 in a subject sample. Additionally, a diagnostic method is provided for evaluating the appearance, status, course, or treatment of lymphocytic leukemia in a subject. A kit is also provided to detect the presence of ROR1 protein comprising the antibody above. Also provided are vaccines and related methods for protecting a subject against diseases that involve expression of ROR1. Humanized antibodies and ROR1 antibody precipitates are also provided.
摘要:
Therapeutic antibodies having binding specificity for ROR-1 expressed on cancer cells (particularly leukemic and lymphomic cells) and pharmaceutical compositions containing one or more such antibodies for use in treating cancer. Methods for diagnosing such cancers through in vitro detection of binding to ROR-1 protein expressed on putative cancer cells are also provided.
摘要:
This invention relates to genes which encode accessory molecule ligands and their use for immunomodulation, vaccination and treatments of various human diseases, including malignancies and autoimmune diseases. This invention also describes the use of accessory molecule ligands which are made up of various domains and subdomain portions of molecules derived from the tumor necrosis factor family. The chimeric molecules of this invention contain unique properties which lead to the stabilization of their activities and thus greater usefulness in the treatment of diseases. Vectors for expressing genes which encode the molecules of this invention are also discussed.
摘要:
The present invention provides for an isolated polynucleotide sequence encoding a chimeric CD154, comprising a first nucleotide sequence encoding an extracellular subdomain of non-human CD154, preferably murine CD154, that replaces a cleavage site of human CD154, and a second nucleotide sequence encoding an extracellular subdomain of human CD154 that binds to a human CD154 receptor. The first nucleotide sequence preferably further encodes an extracellular subdomain of nonhuman CD154 that is critical for expression of said CD154 by cells, such as human CD40+ cells, and another extracellular domain that detects expression of the chimeric CD154 by binding to anti-murine antibodies. The second nucleotide sequence preferably further encodes an extracellular subdomain of human CD154 to which functionally inhibitory anti-CD154 antibodies bind. The present invention also provides for the chimeric CD154 that is encoded by the above-described polynucleotide sequence, an expression vector and a genetic vector comprising the polynucleotide sequence, a host cell comprising the expression vector or the genetic vector, a process for producing the chimeric CD154, and methods for utilizing the expression vectors and genetic constructs containing the chimeric CD154 polynucleotide sequences.