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 cmHsp70.1 monoclonal antibody.
mi-TUMEXdx: A monoclonal antibody recognising membrane Hsp70
Using multimmune's unique monoclonal antibody which recognises 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., Cancer 2007, 110:926-935).
Furthermore, high Hsp70-membrane expression on leukemic cells from patients with acute myeloid leukemia has been shown to be associated with a worse prognosis (Steiner et al., Leukemia 2006, 20: 2076-2070).
mi-lipHsp70dx: An enzyme immunoassay for detecting lipid-associated Hsp70 in the peripheral circulation
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. To quantify free as well as lipid-bound Hsp70 derived from exosomes in the serum of tumor patients, the cmHsp70.1 monoclonal antibody forms the basis to a novel patented lipHsp70 sandwich ELISA. This assay specifically detects the inducible form of Hsp70 and does not cross-react with the highly homologous constitutive form - Hsc70. The antibody used in this assay recognises free and membrane-bound Hsp70 on living tumor cells.
A comparison of the 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., Clinical and Cellular Immunology 2015, 5:5). Furthermore, serum levels of Hsp70 correlate with gross tumor volume in patients with squamous cell and adeno non-small cell lung cancer (Gunther et al., Frontiers in Immunology 2015, 6:556).
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).