Polynucleotides related to monoclonal antibody 1A7 and use for the treatment of melanoma and small cell carcinoma

DETAILED DESCRIPTION This invention relates to the discovery of an anti-idiotype antibody that is capable of recruiting a tumor-specific response against GD2.
The antibody is designated 1A7.
The immune response elicited by 1A7 typically comprises both humoral and cellular components, and is therefore expected to be useful in palliating the clinical conditions related to GD2-associated tumors.
The invention comprises the 1A7 antibody molecule, along with polynucleotide and polypeptide derivatives thereof, and methods for using these compounds in diagnosis and treatment.
Cancer patients are typically tolerized to various tumor associated antigens (TAA), including GD2.
1A7 successfully circumvents immune tolerance, and elicits an immune response against GD2.
According to the network theory, Ab1 represents anti-tumor monoclonal antibody; Ab2 represents anti-idiotypic monoclonal antibody; and Ab3 represents anti-anti-idiotypic monoclonal antibody.
1A7 is an Ab2 that stimulates Ab3 with the same specificity as Ab1, and can therefore recruit effector functions against tumors bearing the tumor antigen.
An Ab3 response reactive against the original TAA is referred to herein as Ab1'.
While not wishing to be bound by theory, one explanation is that the 1A7 combining site may present a region that at least partly resembles an epitope in GD2 in the context of one or more other epitopes which render it more immunogenic.
The epitope of GD2 which may resemble that of 1A7 is identified by the Ab1 (14G2a) used to generate 1A7.
As a result, 1A7 escapes the normal immune tolerance against GD2, and is able to elicit an anti-GD2 response.
FIGS.
1 and 2 show the nucleotide encoding region of the 1A7 light and heavy chain variable regions, respectively, along with the corresponding amino acid translation.
These sequences were compared with those of other known immunoglobulin molecules (Example 2).
Both the polynucleotide and polypeptide variable region sequences for 1A7 are unique.
Amongst the 50 database sequences matched most closely to that of the 1A7 light chain variable region, none was identical