Discernible cell surface protein variants of cd117 for use in cell therapy
AssigneesUniversitäT Basel, Cimeio Therapeutics AG
InventorsStefanie URLINGER, Rosalba LEPORE, Lukas JEKER, Amélie WIEDERKEHR, Alessandro SINOPOLI, Anna CAMUS, Lisa WELLINGER, Romina MATTER-MARONE
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Abstract
The present disclosure relates to the use of cells having discernible surface protein with engineered or naturally occurring mutation(s) but functional surface protein for use in therapy. The present invention also relates to the use of cells having discernible CD117 surface protein variants but functional surface protein for use in therapy, in particular adoptive cell therapy.
Claims24
A mammalian cell or a population of cells expressing a first isoform of CD117 for use in a medical treatment in a patient in need thereof, said patient having cells expressing a second isoform of CD117,
- wherein said cell expressing said first isoform comprises genomic DNA with at least one polymorphism or genetically engineered allele,
- wherein said polymorphism or genetically engineered allele is not present in the genome of the patient having cells expressing said second isoform of CD117,
- wherein said polymorphic or genetically engineered allele is characterized by at least one substitution of an amino acid in position E73, D121, R122, S123, S239, Y259 and/or S261 of SEQ ID NO:
- 1.
A depleting agent for use in preventing or reducing the risk of severe side effects in a patient having received a cell expressing a first isoform of CD117, wherein said patient's native cells express a second isoform of CD117, and wherein said depleting agent comprises at least a second antigen-binding region which binds specifically to said first isoform of CD117 and does not bind or binds substantially weaker to said second isoform of CD117.
A depleting agent for use in selectively depleting the host cells in a patient in need thereof wherein said patient's native cells express a second isoform of CD117 and wherein said depleting agent comprises at least a antigen-binding region which binds specifically to said second isoform of CD117, and wherein said first antigen-binding region of said depleting binds specifically to an epitope including the amino acids E73, D121, R122, S123, S239, Y259 and/or S261 of SEQ ID NO:
- 1, more preferably to an epitope including the amino acids E73, S123, K127 and/or Y259 of SEQ ID NO:
- 1.
A combination of
- a) a mammalian cell or a population of cells expressing an isoform of CD117, wherein said isoform of CD117 is characterized by a substitution of the aspartic acid at position 121 of wild type CD117 to a lysine, and
- b) a depleting agent comprising
- i. an antibody heavy chain variable domain (VH) comprising the three CDRs VHCDR1, VHCDR2 and VHCDR3 wherein VHCDR1 is SEQ ID NO:
- 17, VHCDR2 is SEQ ID NO:
- 18 and VHCDR3 is SEQ ID NO:
- 19, and
- an antibody light chain variable domain (VL) comprising the three CDRs VLCDR1, VLCDR2 and VLCDR3 wherein VLCDR1 is SEQ ID NO:
- 20, VLCDR2 is SEQ ID NO:
- 21 and VLCDR3 is SEQ ID NO:
- 22,
- ii. an antibody heavy chain variable domain (VH) comprising the three CDRs VHCDR1, VHCDR2 and VHCDR3 wherein VHCDR1 is SEQ ID NO:
- 17, VHCDR2 is SEQ ID NO:
- 18 and VHCDR3 is SEQ ID NO:
- 19, and
- an antibody light chain variable domain (VL) comprising the three CDRs VLCDR1, VLCDR2 and VLCDR3 wherein VLCDR1 is SEQ ID NO:
- 59, VLCDR2 is SEQ ID NO:
- 21 and VLCDR3 is SEQ ID NO:
- 60, or
- iii. an antibody heavy chain variable domain (VH) comprising the three CDRs VHCDR1, VHCDR2 and VHCDR3 wherein VHCDR1 is SEQ ID NO:
- 17, VHCDR2 is SEQ ID NO:
- 18 and VHCDR3 is SEQ ID NO:
- 19, and
- an antibody light chain variable domain (VL) comprising the three CDRs VLCDR1, VLCDR2 and VLCDR3 wherein VLCDR1 is SEQ ID NO:
- 59, VLCDR2 is SEQ ID NO:
- 21 and VLCDR3 is SEQ ID NO:
- 61.
- for use in a medical treatment in a patient in need thereof.
A combination of
- a) a mammalian cell or a population of cells expressing an isoform of CD117, wherein said isoform of CD117 is characterized by a substitution of the serine at position 123 of wild type CD117 to a lysine, and
- b) a depleting agent comprising
- i. an antibody heavy chain variable domain (VH) comprising the three CDRs VHCDR1, VHCDR2 and VHCDR3 wherein VHCDR1 is SEQ ID NO:
- 17, VHCDR2 is SEQ ID NO:
- 18 and VHCDR3 is SEQ ID NO:
- 19, and
- an antibody light chain variable domain (VL) comprising the three CDRs VLCDR1, VLCDR2 and VLCDR3 wherein VLCDR1 is SEQ ID NO:
- 20, VLCDR2 is SEQ ID NO:
- 21 and VLCDR3 is SEQ ID NO:
- 22,
- ii. an antibody heavy chain variable domain (VH) comprising the three CDRs VHCDR1, VHCDR2 and VHCDR3 wherein VHCDR1 is SEQ ID NO:
- 17, VHCDR2 is SEQ ID NO:
- 18 and VHCDR3 is SEQ ID NO:
- 19, and
- an antibody light chain variable domain (VL) comprising the three CDRs VLCDR1, VLCDR2 and VLCDR3 wherein VLCDR1 is SEQ ID NO:
- 59, VLCDR2 is SEQ ID NO:
- 21 and VLCDR3 is SEQ ID NO:
- 60, or
- iii. an antibody heavy chain variable domain (VH) comprising the three CDRs VHCDR1, VHCDR2 and VHCDR3 wherein VHCDR1 is SEQ ID NO:
- 17, VHCDR2 is SEQ ID NO:
- 18 and VHCDR3 is SEQ ID NO:
- 19, and
- an antibody light chain variable domain (VL) comprising the three CDRs VLCDR1, VLCDR2 and VLCDR3 wherein VLCDR1 is SEQ ID NO:
- 59, VLCDR2 is SEQ ID NO:
- 21 and VLCDR3 is SEQ ID NO:
- 61.
- for use in a medical treatment in a patient in need thereof.
Dependencies are inferred from the claim text.