Chimeric antigen receptors specific for b-cell maturation antigen and encoding polynucleotides
AssigneesJuno Therapeutics, Inc., Memorial Sloan Kettering Cancer Center
InventorsBlythe D. SATHER, Eric L. SMITH
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Abstract
Provided herein are chimeric receptors, such as chimeric antigen receptors (CARs), comprising BCMA-binding molecules, such as anti-BCMA antibodies and antigen-binding fragments thereof, such as heavy chain variable (VH) regions and single-chain antibody fragments, and encoding polynucleotides. In some embodiments, the anti-BCMA chimeric receptors specifically bind to BCMA. Among the anti-BCMA-binding molecules are human antibodies, including those that compete for binding to BCMA with reference antibodies, such as a non-human reference antibody. Also provided are genetically engineered cells expressing the CARs and uses thereof such as in adoptive cell therapy.
Claims51
1-275. (canceled)
A chimeric antigen receptor comprising:
- (a) an extracellular antigen-binding domain that specifically recognizes B cell maturation antigen (BCMA);
- (b) a spacer of at least 125 amino acids in length;
- (c) a transmembrane domain;
- and (d) an intracellular signaling region.
A polynucleotide encoding a chimeric antigen receptor, comprising nucleic acid encoding:
- (a) an extracellular antigen-binding domain that specifically recognizes an antigen;
- (b) a spacer of at least 125 amino acids in length;
- (c) a transmembrane domain;
- and (d) an intracellular signaling region, wherein following expression of the polynucleotide in a human cell, the transcribed RNA, from the polynucleotide, exhibits at least 70% RNA homogeneity.
A method of determining the heterogeneity of a transcribed nucleic acid of a transgene, the method comprising:
- a) amplifying a transcribed nucleic acid using at least one 5′ and 3′ primer pair, wherein at least one pair comprises a 5′ primer that is complementary to a nucleic acid sequence within the 5′ untranslated region (5′ UTR) of the transcribed nucleic acid and a 3′ primer that is complementary to a nucleic acid sequence within the 3′ untranslated region (3′ UTR) of the transcribed nucleic acid to generate one or more amplified products;
- and
- b) detecting the amplified products, wherein the presence of two or more amplified products from at least one 5′ and 3′ primer pair indicates heterogeneity in the amplified products.
Dependencies are inferred from the claim text.