A compound being developed to treat eye disease also kills leukemia cells

An active ingredient in eye drops that were being developed for the treatment of a form of eye disease has shown promise for treating an aggressive form of blood cancer. Scientists at the Wellcome Sanger Institute, University of Cambridge, University of Nottingham and their collaborators have found that this compound, which targets an essential cancer gene, could kill leukemia cells without harming non-leukemic blood cells.

The results was published in Nature Communications reveal a potential new treatment approach for an aggressive blood cancer with a poor prognosis.

Acute myeloid leukemia (AML) is a form of blood cancer that affects people of all ages, often requiring months of intensive chemotherapy and prolonged hospital admissions. It develops in cells in the bone marrow crowding out the healthy cells, in turn leading to life-threatening infections and bleeding.

Mainstream AML treatments have remained unchanged for over thirty years, with the current treatment being chemotherapy, and the majority of people's cancer cannot be cured. A subtype of AML, driven by rearrangements in the MLL gene has a particularly bad prognosis.

In a previous study, researchers at the Sanger Institute developed an approach, based on CRISPR gene editing technology, which helped them identify more than 400 genes as possible therapeutic targets for different subtypes of AML. One of the genes, SRPK1, was found to be essential for the growth of MLL-rearranged AML. SRPK1 is involved in a process called RNA splicing, which prepares RNA for translation into proteins, the molecules that conduct the majority of normal cellular processes, including growth and proliferation.

In a new study, Sanger Institute researchers and their collaborators set out to work out how inhibition of SRPK1 can kill AML cells and whether it has therapeutic potential in this disease. They first showed that genetic disruption of SRPK1 stopped the growth of MLL-rearranged AML cells and then went on to study the compound SPHINX31, an inhibitor of SRPK1, which was being used to develop an eye drop treatment for retinal neovascular disease -- the growth of new blood vessels on the retinal surface that bleed spontaneously and cause vision loss.

The team found that the compound strongly inhibited the growth of several MLL-rearranged AML cell lines, but did not inhibit the growth of normal blood stem cells. They then transplanted patient-derived human AML cells into immunocompromised mice and treated them with the compound. Strikingly, the growth of AML cells was strongly inhibited and the mice did not show any noticeable side effects.

Dr George Vassiliou, Wellcome Sanger Institute and the Wellcome-MRC Cambridge Stem Cell Institute, said: "We have discovered that inhibiting a key gene with a compound being developed for an eye condition can stop the growth of an aggressive form of acute myeloid leukemia without harming healthy cells. This shows promise as a potential approach for treating this aggressive leukemia in humans."

SRPK1 controls the splicing* of RNA in the production of new proteins. An example of a gene that is affected when SRPK1 is blocked is BRD4, a well-known gene that maintains AML. Inhibiting SRPK1 causes the main form of BRD4 to switch to another form, a change that is detrimental to AML growth.

Dr Konstantinos Tzelepis, the Wellcome Sanger Institute and University of Cambridge, said: "Our study describes a novel mechanism required for leukemia cell survival and highlights the therapeutic potential of SRPK1 inhibition in an aggressive type of AML. Targeting this mechanism may be effective in other cancers where BRD4 and SRPK1 play a role, such as metastatic breast cancer."

Professor David Bates, University of Nottingham and co-founder of biotech company Exonate, which develops eye drops for retinal diseases, said: "When Dr Vassiliou told me that SRPK1 was required for the survival of a form of AML, I immediately wanted to work with him to find out if our inhibitors could actually stop the leukemia cells growing. The fact that the compound worked so effectively bodes well for its potential development as a new therapy for leukemia. It will take some time, but there is real promise for a new treatment on the horizon for patients with this aggressive cancer."

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Engineered cancer cells can fight primary and metastatic cancer

What if cancer cells could be re-engineered to turn against their own kind?

A new study led by researchers from Brigham and Women's Hospital : The power of gene editing to take a critical step toward using cancer cells to kill cancer. The reports were promising results in preclinical models across multiple types of cancer cells, establishing a potential roadmap toward clinical translation for treating primary, recurrent and metastatic cancer.

"This is just the tip of the iceberg. Cell-based therapies hold tremendous promise for delivering therapeutic agents to tumors and may provide treatment options where standard therapy has failed. With our technique, we show it is possible to reverse-engineer a patient's own cancer cells and use them to treat cancer. We think this has many implications and could be applicable across all cancer cell types."        says  Dr.Khalid Shah,Director of the Center for Stem Cell Therapeutics and Imaging (CSTI) , BWH Department of Neurosurgery and Faculty at Harvard Medical School and Harvard Stem Cell Institute (HSCI).

The new approach capitalizes on cancer cells' self-homing ability that process in which cancer cells can track the cells of their kind that have spread within the same organ or to other parts of the body. Harnessing this power could overcome drug delivery challenges, helping get therapeutics to tumor sites that may otherwise be difficult to reach.

The team developed and tested two techniques to harness the power of cancer cells. The "off the shelf" technique used pre-engineered tumor cells that would need to be matched to a patient's HLA phenotype and the second technique "autologous" which uses CRISPR technology to edit the genome of a patient's cancer cells and insert therapeutic molecules. These cells could then be transferred back into the patient.

To test both approaches, they used mouse models of primary and recurrent brain cancer and breast cancer that has spread to the brain. They saw a direct migration of engineered cells to the sites of tumors and found evidence that the engineered cells specifically targeted and killed recurrent and metastatic cancer in the mice which in turn treatment increased the survival of the mice. Engineered cells were equipped with a "kill switch" that could be activated after treatment -- PET imaging showed that this kill switch worked to eliminate the cells.

"Our study demonstrates the therapeutic potential of using engineered tumor cells and their self-homing properties for developing receptor-targeted therapeutics for various cancers," said Shah.

Our conference Cell Tissue Science 2019, mainly focuses on the complications the consequences of  Cancer Cell Biology and Technical Advancements in cancer treatment. The speakers from different part of the world will be present their immense research talk on this specific topics. We welcome you to the our upcoming conference “ 12th World Congress on Cell & Tissue Science” .You can also present your latest research at our conference.For more info visit : Celltissue Science 2019