Methods for treating neuroblastoma with combination therapy
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Publication Number
US-12435156-B2
Publication Date
2025-10-07
Expiration Date
Abstract
The present disclosure provides methods of treating neuroblastoma using an anti-GD2 antibody, at least one chemotherapeutic agent, and at least one hematopoietic growth factor. The present disclosure also provides compositions for treating neuroblastoma.
Core Innovation
The invention relates to a method of treating a human subject having chemoresistant neuroblastoma by administering an anti-GD2 antibody, or an antigen-binding fragment thereof, together with at least one hematopoietic growth factor, irinotecan, and temozolomide. The approach is directed to anti-GD2 targeting of a GD2 tumor antigen associated with neuroblastoma, including chemoresistant disease such as refractory and relapsed neuroblastoma.
The anti-GD2 antibody, and antigen-binding fragments thereof, is defined by specific heavy chain variable region and light chain variable region characteristics. In the disclosed embodiments, a humanized 3F8 antibody (hu3F8) with heavy/light CDR residue ranges and SEQ ID homology is employed, with conservative modifications contemplated within the antibody definition.
The disclosed combination includes hematopoietic growth factors such as G-CSF and/or GM-CSF, including recombinant GM-CSF sargramostim, combined with topoisomerase I inhibition via irinotecan and alkylation via temozolomide. The document further describes cyclic administration and associated clinical evaluation, including reporting response outcomes in chemoresistant high-risk neuroblastoma and discussing MRD monitoring using circulating tumor-associated cell-free RNA (cfRNA) with qRT-PCR.
Claims Coverage
The provided partial content identifies one independent claim. The independent claim covers treatment of chemoresistant neuroblastoma using a defined anti-GD2 antibody, or antigen-binding fragment, in combination with a hematopoietic growth factor plus irinotecan and temozolomide, with the antibody defined by specified heavy- and light-chain CDR residue ranges.
Treatment of chemoresistant neuroblastoma with anti-GD2 plus hematopoietic growth factor and irinotecan/temozolomide
A method of treating a human subject having chemoresistant neuroblastoma by administering a therapeutically effective amount of an anti-GD2 antibody, or antigen-binding fragment, together with at least one hematopoietic growth factor, irinotecan, and temozolomide.
Anti-GD2 antibody defined by heavy-chain and light-chain CDR residue ranges to SEQ ID NO:4 and SEQ ID NO:5
The anti-GD2 antibody, or antigen-binding fragment, has a heavy chain variable region comprising CDR1 residues 31 to 35 of SEQ ID NO:4, CDR2 residues 50 to 65 of SEQ ID NO:4, and CDR3 residues 98 to 108 of SEQ ID NO:4, and a light chain variable region comprising CDR1 residues 24 to 34 of SEQ ID NO:5, CDR2 residues 50 to 56 of SEQ ID NO:5, and CDR3 residues 89 to 94 of SEQ ID NO:5.
Anti-GD2 antibody defined by heavy-chain CDR residue ranges to SEQ ID NO:11 and light-chain CDRs to SEQ ID NO:5
The anti-GD2 antibody, or antigen-binding fragment, has a heavy chain variable region comprising CDR1 residues 31 to 35 of SEQ ID NO:11, CDR2 residues 50 to 65 of SEQ ID NO:11, and CDR3 residues 98 to 108 of SEQ ID NO:11, and a light chain variable region comprising CDR1 residues 24 to 34 of SEQ ID NO:5, CDR2 residues 50 to 56 of SEQ ID NO:5, and CDR3 residues 89 to 94 of SEQ ID NO:5.
The inventive coverage centers on administering a therapeutically effective anti-GD2 antibody, or antigen-binding fragment, for chemoresistant neuroblastoma, combined with at least one hematopoietic growth factor, irinotecan, and temozolomide, while defining the antibody by specified heavy- and light-chain CDR residue ranges.
Stated Advantages
Not explicitly described in patent.
Documented Applications
Treatment of a human subject having chemoresistant neuroblastoma, including refractory and relapsed neuroblastoma, using a combination chemoimmunotherapy including an anti-GD2 antibody, hematopoietic growth factor(s), irinotecan, and temozolomide.
Non-invasive MRD monitoring using circulating tumor-associated cfRNA with qRT-PCR for neuroblastoma.
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