multimmune's goal is to build a well-staged pipeline of differentiated products for identifying patients that will respond to membrane Hsp70-directed therapies, for the diagnosis and prognosis of cancer, and for the monitoring of therapeutic responses to anti-cancer therapies.
multimmune's lead mi-DIAGNOSTICS (dx) candidates are a patented monoclonal antibody for detecting the presence of tumors expressing the membrane form of Hsp70, and a patented enzyme immunoassay for the detection of lipid-associated Hsp70 in the peripheral circulation which is based on multimmune's unique proprietary cmHsp70.1 monoclonal antibody.
mi-TUMEXdx: A monoclonal antibody recognition membrane Hsp70
Using multimmune's unique monoclonal antibody which recognizes the membrane form of Hsp70 which is expressed on cancer cells, an Hsp70 membrane-positive phenotype was found in 40% (colon), 37% (gastric), 43% (lower rectal), and 42% (squamous cell) of the analyzed tumor specimens. None of the corresponding normal tissues was found to be Hsp70 membrane-positive. In patients with colon ( P = .032) and gastric ( P = .045) carcinomas, an Hsp70 membrane expression correlated significantly with an improved overall survival; a negative association was seen in lower rectal ( P = .085) and squamous cell carcinoma (P = .048) (Pfister et al., 2007).
Furthermore, high Hsp70 membrane expression on leukemic cells from patients with acute myeloid leukemia has been shown to be associated with a poorer prognosis (Steiner et al., 2006).
mi-Hsp70-ex: A Companion Diagnostic (CDx) for detecting tumors expressing membrane Hsp70 and monitoring therapeutic response
Elevated levels of the stress-inducible heat shock protein 70 (Hsp70) in the peripheral circulation have been reported for many tumor entities. We have shown that Hsp70 membrane-positive tumor cells actively release Hsp70 in exosome-like lipid vesicles. We have developed a simple assay to quantify the levels of 'free' and 'exosomal' Hsp70 in the circulation of patients with cancer which uses multimmune's unique, proprietary monoclonal antibodies (patent application filed) .
A comparison of exosomal Hsp70 levels in patients with head and neck, lung, colorectal, pancreatic cancer, glioblastoma or hematological malignancies and healthy human volunteers has revealed significantly higher levels in tumor patients ( Breuninger et al., 2015; Werner et al., 2021). Furthermore, serum levels of lipHsp70 correlate with gross tumor volume in patients with squamous cell and adeno non-small cell lung cancer (Gunther et al., 2015). The assay is also being developed for monitoring therapeutic response and disease recurrence in a number of cancer settings.
Membrane Hsp70 - A novel target for the isolation of circulating tumor cells after Epithelial-to-Mesenchymal Transition
A study published in Frontiers in Oncology has reported on the use of the cmHsp70.1 monoclonal antibody for the isolation of circulating tumor cells (CTCs). The proposition is that this approach is superior to those that employ antibodies against EpCAM (CD326).