SH7139, the first of a series of selective high affinity
ligand (SHAL) oncology
drug candidates designed to target and bind to the
HLA-DR proteins overexpressed by
B-cell lymphomas, has demonstrated exceptional efficacy in the treatment of
Burkitt lymphoma xenografts in mice and a safety profile that may prove to be unprecedented for an oncology
drug. The aim of this study was to determine how frequently the HLA-DRs targeted by
SH7139 are expressed by different subtypes of
non-Hodgkin's lymphoma and by other solid
cancers that have been reported to express
HLA-DR. Binding studies conducted with
SH7129, a biotinylated analog of
SH7139, reveal that more than half of the biopsy sections obtained from patients with different types of
non-Hodgkin's lymphoma express the HLA-DRs targeted by
SH7139. Similar analyses of
tumor biopsy tissue obtained from patients diagnosed with eighteen other solid
cancers show the majority of these
tumors also express the HLA-DRs targeted by
SH7139. Cervical, ovarian, colorectal and
prostate cancers expressed the most
HLA-DR. Only a few esophageal and head and neck
tumors bound the diagnostic. Within an individual's
tumor, cell to cell differences in
HLA-DR target expression varied by only 2 to 3-fold while the expression levels in
tumors obtained from different patients varied as much as 10 to 100-fold. The high frequency with which
SH7129 was observed to bind to these
cancers suggests that many patients diagnosed with
B-cell lymphomas, myelomas, and other non-hematological
cancers should be considered potential candidates for new
therapies such as
SH7139 that target
HLA-DR-expressing
tumors.