Mortalin based Minibody for treating CLL

Summary of the technology

Our objective is to generate a recombinant minibody composed of anti-CD20 single chain antibody linked to mortalin mimetic peptides. It is intended for treatment of hundreds of thousands of patients diagnosed with early stage indolent B-chronic lymphocytic leukemia (CLL). CLL is the most common leukemia in the Western world accounting for about a third of all leukemias in the USA causing about 4,500 deaths a year. In most patients the disease will be indolent, yet a cohort of patients will have a rapid disease progression and poor prognosis. Despite a wide range of treatment options, a substantial number of patients succumb to their disease. Most of the current treatment modalities for CLL are non-specific and impose high risks of adverse outcomes. The therapeutic efficacy of anti-cancer antibodies as single agents has been rather limited and currently the antibodies are being applied in combination with conventional chemotherapy and radiotherapy. The novel recombinant minibody is expected to potentiate the anti-cancer effect of anti-CD20 antibodies and of other conventional therapies. Due to its selectivity to CD20-positive cells, the off target effects of this novel biotherapy are expected to be minimal. It is conceivable to assume that treatment at the early phase with an effective yet non-toxic therapy will enhance the prospect to achieve complete cure from CLL.
Project ID : 10-2014-822

Details of the Technology Offer

Mortalin (also known as GRP75 and mitochondrial Hsp70) is a ubiquitously expressed mitochondrial chaperone related to the cytosolic heat shock protein 70 (HSP70). It protects cells from senescence and apoptosis and is overexpressed in cancer cells. We discovered that cell resistance to complement-dependent cytotoxicity depends on mortalin and that mortalin is released from cells during complement attack (Pilzer and Fishelson, Int. Immunol. 2005; Pilzer et al. Int. J. Cancer 2010). We have investigated whether or not colorectal cancer patients have circulating mortalin in their blood. To this end, we developed a sensitive ELISA for mortalin.
We have tested (in Tel Aviv) the levels of mortalin in serum samples (collected in Budapest) from 2 large cohorts of CRC patients. The levels of soluble Hsp70 were also determined in these patients’ sera by using a commercial Hsp70 ELISA. The significance of mortalin and Hsp70 in blood to survival prospects of the colorectal cancer patients was evaluated in two independent studies. The findings of the 2 studies, separately and collectively, showed that high levels of mortalin and Hsp70 were found in the blood of early and late stage CRC patients with the shorter survival time.

Project manager

Adi Elkeles
BD Manager

Project researchers

Zvi Fishelson
T.A.U Tel Aviv University, Medicine-Sackler Faculty
Cell and Developmental Biology

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