Radiolabelled antibody and uses thereof
The present disclosure describes a radioconjugate of an anti-CD38 antibody and a radionuclide, e.g., Bi 213 .
1. A radioconjugate comprising an antibody specific for CD38 comprising an HCDR1 region of sequence GFTFSSYYMN (SEQ ID NO: 1) or SYYMN (SEQ ID NO: 14), an HCDR2 region of sequence GIS[ ]GDP[ ]SNTYY[ ]AD[ ]S[ ]VKG (SEQ ID NO: 2), an HCDR3 of sequence DLPLVYTGFAY (SEQ ID NO: 3), an LCDR1 region of sequence SGDNLRHYYVY (SEQ ID NO: 4), an LCDR2 region of sequence GDSKRPS (SEQ ID NO: 5), and an LCDR3 region of sequence QTYTGGASL (SEQ ID NO: 6).
2. The radioconjugate of claim 1 , wherein the HCDR1 region comprises SYYMN (SEQ ID NO: 14).
3. The radioconjugate of claim 1 , wherein the radionuclide comprises an alpha particle emitting isotope.
4. The radioconjugate according to claim 1 , wherein the radionuclide is selected from iodine-131, yttrium-90, lutetium-177, copper-67, astatine-211, bismuth-212, bismuth-213, and actinium-225.
5. The radioconjugate according to claim 4 , wherein the radionuclide is bismuth-213.
6. The radioconjugate according to claim 1 ,
wherein the antibody comprises a variable heavy chain of the sequence QVQLVESGGGLVQPGGSLRLSCAASGFTFSSYYMNWVRQAPGKGLEWVSGISGDPSNTYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCARDLPLVYTGFAYWGQGTLVTVSS (SEQ ID NO: 10) and
a variable light chain of the sequence DIELTQPPSVSVAPGQTARISCSGDNLRHYYWWYQQKPGQAPVLVIYGDSKRPSGIPERFS[ ]GSNSGNTATLTISGTQAEDEADYYCQTYTGGASLVFGGGTKLTVLGQ (SEQ ID NO: 11).
7. The radioconjugate according to claim 1 , wherein the antibody comprises an IgG1 Fc region.
8. The radioconjugate according to claim 1 , wherein the antibody comprises a modified Fc region, wherein said modification enhances ADCC or CDC activity.
9. A method of treating multiple myeloma in an individual in need thereof, comprising administration of a radioconjugate according to claim 1 .
10. The method of claim 9 , wherein the radioconjugate comprises an antibody specific for CD38 comprising an HCDR1 region of sequence GFTFSSYYMN (SEQ ID NO: 1) or of sequence SYYMN (SEQ ID NO: 14), an HCDR2 region of sequence GIS[ ]GDP[ ]SNTYY[ ]AD[ ]S[ ]VKG (SEQ ID NO: 2), an HCDR3 region of sequence DLPLVYTGFAY (SEQ ID NO: 3), an LCDR1 region of sequence SGDNLRHYYVY (SEQ ID NO: 4), an LCDR2 region of sequence GDSKRPS (SEQ ID NO: 5), and an LCDR3 region of sequence QTYTGGASL (SEQ ID NO: 6) and 213Bi.
11. The method of claim 10 , wherein the HCDR1 region of the radioconjugate comprises SYYMN (SEQ ID NO: 14).
12. The method of claim 10 , wherein the radioconjugate comprises an antibody region that comprises a variable heavy chain of the sequence QVQLVESGGGLVQPGGSLRLSCAASGFTFSSYYMNWVRQAPGKGLEWVSGISGDPSNTYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCARDLPLVYTGFAYWGQGTLVTVSS
(SEQ ID NO: 10) and
a variable light chain of the sequence DIELTQPPSVSVAPGQTARISCSGDNLRHYYWWYQQKPGQAPVLVIYGDSKRPSGIPERFS[ ]GSNSGNTATLTISGTQAEDEADYYCQTYTGGASLVFGGGTKLTVLGQ (SEQ ID NO: 11).
13. A method of treating non-hodgkin's lymphoma in an individual in need thereof, comprising administration of a radioconjugate according to claim 1 .
14. The method of claim 13 , wherein the radioconjugate comprises an antibody specific for CD38 comprising an HCDR1 region of sequence GFTFSSYYMN (SEQ ID NO: 1) or of sequence SYYMN (SEQ ID NO: 14), an HCDR2 region of sequence GIS[ ]GDP[ ]SNTYY[ ]AD[ ]S[ ]VKG (SEQ ID NO: 2), an HCDR3 region of sequence DLPLVYTGFAY (SEQ ID NO: 3), an LCDR1 region of sequence SGDNLRHYYVY (SEQ ID NO: 4), an LCDR2 region of sequence GDSKRPS (SEQ ID NO: 5), and an LCDR3 region of sequence QTYTGGASL (SEQ ID NO: 6) and 213Bi.
15. The method of claim 14 , wherein the HCDR1 region of the radioconjugate comprises SYYMN (SEQ ID NO: 14).
16. The method of claim 14 , wherein the radioconjugate comprises an antibody specific for CD38 comprising an HCDR1 region of sequence GFTFSSYYMN (SEQ ID NO: 1) or of sequence SYYMN (SEQ ID NO: 14), an HCDR2 region of sequence GIS[ ]GDP[ ]SNTYY[ ]AD[ ]S[ ]VKG (SEQ ID NO: 2), an HCDR3 region of sequence DLPLWTGFAY (SEQ ID NO: 3), an LCDR1 region of sequence SGDNLRHYYVY (SEQ ID NO: 4), an LCDR2 region of sequence GDSKRPS (SEQ ID NO: 5), and an LCDR3 region of sequence QTYTGGASL (SEQ ID NO: 6) and 213Bi.