Compositions and methods for immunotherapy targeting flt3, pd-1, and/or pd-l1
AssigneeCytoimmune Therapeutics, Inc.
InventorsJianhua Yu, Michael Caligiuri
Life of this patent
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Abstract
CAR cells targeting FLT3 antigens in combination with a secreted anti-PD-1 and anti-PD-L1 antibodies or anti-PD-1-anti-PD-L1 bispecific antibodies are described as a new method of cancer treatment. It is proposed that these combination therapies are safe and effective in patients and can be used to treat human tumors and cancer.
Claims30
An isolated nucleic acid or a vector comprising:
- a. a polynucleotide encoding a chimeric antigen receptor (CAR) comprising:
- (a) an antigen binding domain of an FLT3 antibody;
- (b) a hinge domain;
- (c) a transmembrane domain;
- (d) and an intracellular domain;
- and
- b. a polynucleotide encoding an antibody or antigen binding fragment thereof comprising an antigen binding domain that recognizes and binds PD-1 or PD-L1 or both PD-1 and PD-L1.
(canceled)
(canceled)
-16. (canceled)
-21. (canceled)
-25. (canceled)
-32. (canceled)
(canceled)
An antibody or an antigen binding fragment thereof or a polypeptide comprising either or both of:
- (i) a single chain variable fragment sequence (scFv) comprising an amino acid sequence of (Q V Q L V Q S G V E V K K P G A S V K V S C K A S G Y T F T N Y Y M Y W V R Q A P G Q G L E W M G G I N P S N G G T N F N E K F K N R V T L T T D S S T T T A Y M E L K S L Q F D D T A V Y Y C A R R D Y R F D M G F D Y W G Q G T T V T V S S G G G G S G G G G S G G G G S D I Q M T Q S P S S L S A S V G D R V T I T C R A S Q D V S T A V A W Y Q Q K P G K A P K L L I Y S A S F L Y S G V P S R F S G S G S G T D F T L T I S S L Q P E D F A T Y Y C Q Q Y L Y H P A T F G Q G T K V E I K R (SEQ ID NO:
- 13) or an equivalent thereof, optionally encoded by the nucleotide sequence comprising a nucleic acid sequence (CAGGTCCAATTGGTACAGAGCGGCGTCGAAGTAAAGAAGCCTGGAGCCAGCGTTA AAGTTTCTTGCAAGGCTTCAGGATATACTTTCACTAACTACTATATGTACTGGGTAC GGCAGGCTCCAGGGCAAGGGTTGGAGTGGATGGGAGGGATCAATCCTTCTAACGGC GGCACTAACTTTAACGAAAAATTTAAAAATAGGGTGACCCTCACAACTGACTCAAG TACGACTACAGCATACATGGAACTCAAATCTCTCCAATTCGATGACACGGCTGTCTA TTATTGCGCGAGAAGAGACTATCGCTTCGATATGGGGTTTGATTATTGGGGGCAAGG TACTACGGTTACCGTCAGCTCCGGGGGTGGCGGCTCCGGCGGCGGTGGGTCAGGTG GAGGAGGGTCTGACATTCAGATGACGCAATCCCCAAGCTCTCTGTCCGCGTCAGTGG GCGACCGAGTTACAATCACATGCCGCGCTTCTCAAGATGTGTCAACCGCTGTCGCCT GGTACCAACAGAAGCCTGGGAAGGCCCCTAAGCTTCTCATCTACTCAGCTTCTTTTC TGTACTCAGGGGTACCGTCTAGATTCTCAGGATCCGGTAGTGGGACGGACTTCACAT TGACCATAAGTTCCTTGCAGCCTGAGGATTTCGCTACATATTATTGCCAACAGTACC TTTACCATCCTGCCACTTTTGGCCAGGGTACTAAGGTCGAGATCAAACGG (SEQ ID NO:
- 14)), or an equivalent thereof;
- or
- (ii) a scFv comprising an amino acid sequence (EVQLVESGGGLVQPGGSLRLSCAASGFTFSDSWIHWVRQAPGKGLEWVAWISPYGGST YYADSVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCARRHWPGGFDYWGQGTLVT VSAGGGGSGGGGSGGGGSEIVLTQSPATLSLSPGERATLSCRASKGVSTSGYSYLHWYQ QKPGEAPRLLIYLASYLESGVPARFSGSGSGTDFTLTISSLEPEDFAVYYCQHSRDLPLTF GGGTKVEIK (SEQ ID NO:
- 15)) or an equivalent thereof, optionally encoded by the nucleotide sequence:
- (GAAGTTCAGTTGGTCGAGTCAGGAGGAGGCCTGGTGCAACCCGGGGGCT
- CACTCCGGTTGTCCTGTGCTGCTTCAGGATTTACGTTTTCTGACTCATGG
- ATACATTGGGTGCGCCAAGCCCCGGGCAAGGGGCTGGAATGGGTGGCCTG
- GATCTCTCCGTATGGGGGTTCCACCTACTATGCTGATTCAGTAAAAGGAC
- GGTTCACTATAAGCGCGGATACAAGTAAGAATACTGCCTATCTTCAAATG
- AATTCTCTTCGCGCCGAGGATACAGCGGTATATTATTGCGCTAGACGACA
- TTGGCCAGGGGGCTTTGACTATTGGGGGCAGGGTACTCTTGTGACCGTTA
- GTGCGGGAGGTGGTGGCAGCGGTGGAGGCGGCTCCGGGGGTGGTGGTTCA
- GAAATTGTCCTGACTCAATCCCCTGCCACATTGAGTTTGAGCCCAGGAGA
- GAGAGCAACTCTGTCATGCCGGGCGTCAAAAGGTGTCAGTACGTCAGGCT
- ACTCCTATCTTCATTGGTATCAGCAGAAACCGGGAGAAGCGCCGCGCCTT
- CTCATATACCTGGCTAGTTACCTTGAGAGTGGCGTCCCGGCCCGGTTTAG
- TGGGAGTGGGTCTGGGACTGATTTTACGCTGACAATCAGCAGTCTTGAGC
- CAGAGGACTTCGCGGTTTACTATTGCCAACATTCACGCGATTTGCCCCTC
- ACCTTCGGCGGTGGAACGAAGGTTGAAATAAAA (SEQ ID NO:
- 16)), or an equivalent thereof.
-58. (canceled)
(canceled)
-70. (canceled)
Dependencies are inferred from the claim text.