Oncotarget

Research Papers:

Therapeutic applications of the selective high affinity ligand drug SH7139 extend beyond non-Hodgkin’s lymphoma to many other types of solid cancers

Rod Balhorn _ and Monique Cosman Balhorn

PDF  |  Full Text  |  How to cite  |  Press Release

Oncotarget. 2020; 11:3315-3349. https://doi.org/10.18632/oncotarget.27709

Metrics: PDF 1178 views  |   Full Text 2165 views  |   ?  


Abstract

Rod Balhorn1 and Monique Cosman Balhorn1

1 SHAL Technologies Inc., Livermore, CA 94550, USA

Correspondence to:

Rod Balhorn,email: [email protected]

Keywords: HLA-DR; selective high affinity ligand; SH7139; SH7129; solid cancers

Received: March 09, 2020     Accepted: July 27, 2020     Published: September 01, 2020

ABSTRACT

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.


Creative Commons License All site content, except where otherwise noted, is licensed under a Creative Commons Attribution 4.0 License.
PII: 27709