US 2026/0209356 A1Published application

Igg derived b7-h3-specific chimeric antigen receptor (b7-h3 car) effector cells for the treatment of cd276+ tumors and autoimmune diseases

OwnerFranco LOCATELLI, Concetta QUINTARELLI +5inventors

InventorsFranco LOCATELLI, Concetta QUINTARELLI, Biagio DE ANGELIS, Ignazio CARUANA, Lorenzo MORETTA, Cristina BOTTINO, Roberta CASTRICONI

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Abstract

The present invention concerns a vector including the cassette coding for B7-H3 CAR gene obtained using the single chains variable fragments (scFv) of the monoclonal IgG antibody NE97, a method for the production thereof and B7-H3 CAR genetically modified effector cells (such as T cells or innate cells such as NK and NK-T cells) for the treatment of CD276 (B7-H3) positive tumors such as lymphoid malignancies, leukemia and solid tumors such as CNS tumors, extra-cranial and intracranial tumors and autoimmune diseases.

Claims25

Dependent claims

1) Anti-B7-H3 chimeric antigen receptor comprising or consisting of, from the N-terminus to the C-terminus:

a) a signal peptide,
b) an anti B7-H3 single chain antibody domain,
c) a hinge,
d) a trans membrane domain,
e) a co-stimulatory signaling domain, and
f) CD3Zeta chain sequence,
wherein said anti B7-H3 single chain antibody domain comprises of anti B7-H3 NE97 hybridoma VL sequence and anti B7-H3 NE97 hybridoma VH sequence linked each other by a linker, and wherein
anti B7-H3 NE97 hybridoma VL sequence comprises CDR1 sequence EIIYSY (SEQ ID NO:1), CDR2 sequence NAK and CDR3 sequence QHHYGTPPYT (SEQ ID NO:2), whereas
anti B7-H3 NE97 hybridoma VH sequence comprises CDR1 sequence GFTFSSYG (SEQ ID NO:3), CDR2 sequence INSGGSYI (SEQ ID NO:4) and CDR3 sequence ARHEGLPLDY (SEQ ID NO:5).

6 more elements

8) Anti-B7-H3 chimeric antigen receptor according to anyone of claims 1-7, wherein the co-stimulatory signaling domain is chosen from the group consisting of

CD28 cytoplasmic sequence:
(SEQ ID NO:
21)
RSKRSRLLHSDYMNMTPRRPGPTRKHYQPYAPPRDFAAYRS,
CD137 (4-1BB) sequence:
(SEQ ID NO:
22)
KRGRKKLLYIFKQPFMRPVQTTQEEDGCSCRFPEEEEGGCEL,
OX40 sequence:
(SEQ ID NO:
23)
RDQRLPPDAHKPPGGGSFRTPIQEEQADAHSTLAKI,
a sequence obtained by linking
CD28 cytoplasmic sequence:
(SEQ ID NO:
21)
RSKRSRLLHSDYMNMTPRRPGPTRKHYQPYAPPRDFAAYRS
to
CD137 (4-1BB) sequence:
(SEQ ID NO:
22)
KRGRKKLLYIFKQPFMRPVQTTQEEDGCSCRFPEEEEGGCEL,
or
a sequence obtained by linking
CD28 cytoplasmic sequence:
(SEQ ID NO:
21)
RSKRSRLLHSDYMNMTPRRPGPTRKHYQPYAPPRDFAAYRS,
to
OX40 sequence:
(SEQ ID NO:
23)
RDQRLPPDAHKPPGGGSFRTPIQEEQADAHSTLAKI.
9) Anti-B7-H3 chimeric antigen receptor
according to anyone of claims 1-8, wherein
CD3-Zeta chain is
(SEQ ID NO:
24)
RVKFSRSADAPAYQQGQNQLYNELNLGRREEYDVLDKRRGRDPEMGGKPR
RKNPQEGLYNELQKDKMAEAYSEIGMKGERRRGKGHDGLYQGLSTATKDT
YDALHMQALPPR*.

38 more elements

Dependencies are inferred from the claim text.

Facts

Application: 19/139,433Filed 13 Dec 2023
Priority: IT 10202200002559614 Dec 2022
Published: 23 Jul 2026
Term ends: Not estimatedThe source records don’t support an estimate.

Classification31 codes

C07K 16/2827
Against the immunoglobulin superfamily: against B7 molecules, e.g. CD80, CD86
A61K 40/11
Characterised by the cell type used: t-cells, e.g. tumour infiltrating lymphocytes [TIL] or regulatory T [Treg] cells; Lymphokine-activated killer…
A61K 40/31
Characterised by the recombinant expression of specific molecules in the cells of the immune system: chimeric antigen receptors [CAR]
A61K 40/421
Receptors, cell surface antigens or cell surface determinants: immunoglobulin superfamily