Abstract B06: Similarity in breast cancer diversity: A novel target for breast cancer therapy
Authors: Lebowitz Michael S. , Fuller Steven , Ghanbari Hossein A. 
Published: August 2018

There is cancer; there is breast cancer (BCA); then there is luminal-A BCA, luminal-B BCA, HER2-enriched BCA, triple-negative/basal-like BCA; and, yes, normal-like BCA. In each of these distinct forms of BCA, unique targetable vulnerabilities in the tumors’ biologic makeup have been exploited, in many cases rather successfully, for drug development. To be sure, this divide and conquer approach has worked to a point. However, limitations include the targeting of proteins that, while overexpressed in a particular cancer, are also found in normal cells and the fact that many of these targets appear in very small subsets of BCA and thus the need to extensively type each cancer and to treat each individual cancer in a very specific fashion.

Here, we are proposing another time-proven success strategy: unite and govern. We are targeting a commonality within the diverse array of breast cancers: the ASPH gene and its product, human aspartyl (asparaginyl) β-hydroxylase (HAAH). This enzyme has been detected specifically in more than 90% of all breast cancers by immunostaining (IHC/ICC), gene expression analysis (RT-PCR), and immunoassay (serum ELISA). When normal cells are transfected with ASPH, as HAAH is produced and translocated to the surface, they undergo malignant transformation and when ASPH is silenced in tumor cells, they revert to normal phenotype. Moreover, HAAH has a pivotal role in cell proliferation, motility, and invasiveness, the hallmarks of cancer. Also, the HAAH level in tumors is directly correlated with severity of disease and patient survival. HAAH is an embryonic enzyme silenced post-birth, and as such it is a self-protein. We have designed, produced, tested, manufactured, and are now clinically evaluating an HAAH-targeting therapeutic vaccine. This vaccine has effectively overcome self-tolerance and has the ability to become the ultimate cancer immunotherapy agent. In syngeneic rodent models, it is highly immunogenic, and in challenge models using various cell lines, including BCA lines, it has been effective in preventing tumor growth (up to 100%), reducing tumor size (over 90%), controlling metastasis (to over 80%), and increasing survival (to 100%). Even using a full human dose (40 μg total protein), no animal toxicities were reported (FDA-reviewed protocol). The vaccine is introduced intradermally using 3M’s hollow microneedle array device. In the ongoing phase I clinical trial, to date there have been no adverse complications or side effects reported. Furthermore, the vaccine has been demonstrated to be significantly immunogenic. We are now planning phase 2 clinical trials and propose to use this therapeutic cancer vaccine in HAAH-positive breast cancer patients (as high as 90% of all breast cancers). We intend to extend the clinical trials ultimately to all HAAH-positive cancer patients.

Citation Format: Michael S. Lebowitz, Steven Fuller, Hossein A. Ghanbari. Similarity in breast cancer diversity: A novel target for breast cancer therapy [abstract]. In: Proceedings of the AACR Special Conference: Advances in Breast Cancer Research; 2017 Oct 7-10; Hollywood, CA. Philadelphia (PA): AACR; Mol Cancer Res 2018;16(8_Suppl):Abstract nr B06.