US 12,447,218 B1 · Radioconjugates directed to MHC-complexed antigens in cancer

Abstract

Radionuclide-labeled soluble biologics directed against peptide presenting Major Histocompatibility Complexes (pMHCs), and methods for treating cancers using the biologics are provided. Soluble biologics include recombinant T-cell receptor proteins (rTCR) and TCR-antibody mimics that specifically bind to pMHCs. The soluble biologics may further include a heavy chain of IgG1, IgG2, IgG4, or variants thereof. The radioisotopes used to label the soluble biologic may include alpha-emitting isotopes, such as actinium-225, or beta-emitting isotopes, such as lutetium-177, and may be administered at a maximum tolerated dose in a single bolus or in fractionated doses that together equal the maximum tolerated dose. The methods may further include administration of additional therapeutic agents or modalities.

Claims4

Dependent claims

A method for treating a cancer in a human subject, comprising administering a composition consisting essentially of an effective amount of a radiolabeled antibody comprising:

an antibody component comprising the complementarity determining regions (CDRs):
CDRH1 comprising amino acid sequence
(SEQ ID NO:
177)
DYAMH,
CDRH2 comprising amino acid sequence
(SEQ ID NO:
178)
GISWNSGSIGYADSVKG,
CDRH3 comprising amino acid sequence
(SEQ ID NO:
179)
GRGFHYYYYGMDI,
CDRL1 comprising amino acid sequence
(SEQ ID NO:
180)
GGNNIGSRSVH,
CDRL2 comprising amino acid sequence
(SEQ ID NO:
181)
DDSDRPS, and
CDRL3 comprising amino acid sequence
(SEQ ID NO:
182)
QVWDSRTDHWV;
a chelator chemically conjugated to the antibody component, wherein the chelator is DOTA or a DOTA derivative;
and
225Ac radionuclide chelated by the chelator.

25 more elements

Dependencies are inferred from the claim text.

Radioconjugates directed to MHC-complexed antigens in cancer

Life of this patent

Radioconjugates directed to MHC-complexed antigens in cancer

Life of this patent

Abstract

Claims4