'Magic bullet' found in fight against leukemia

'Magic bullet' found in fight against leukemia
High sialic acid-binding immunoglobulin-like lectin (Siglec)-15 surface expression on circulating blood cells from patients with acute myeloid leukaemia (AML). Cell surface expression of Siglec-15 on peripheral blood leucocyte preparations from the peripheral blood of patients with AML. Nine out of 12 patients with AML showed significant cell surface expression of Siglec-15 compared to healthy peripheral blood leucocytes. (A) Representative plots from ‘Patient A’ showing high levels of cell-surface Siglec-15 expression on AML blasts [36% of all peripheral blood mononuclear cells (PBMCs)]. Siglec-15 is co-expressed with CD14 and human leucocyte antigen-DR isotype (HLA-DR). Negative control: mouse immunoglobulin G1 (IgG1) isotype antibody. (B) Representative plots (left panels) from ‘Patient B’ showing negative cell surface staining for CD33 on AML blasts, although 20% of blasts are positive for Siglec-15. Histograms (right panels) comparing cell surface expression of CD33 and Siglec-15 on AML blasts from ‘Patient B’ (isotype control staining, filled histograms; anti-CD33/Siglec-15 antibody staining, open histograms). (C) Representative plots from ‘Patient C’ showing 10% of AML blasts express Siglec-15 on the cell surface, most of which were CD33+CD14+HLA-DR−. (D) Percentage of total circulating PBMCs expressing cell-surface Siglec-15 from 14 patients with AML (open circles) and nine healthy donors (solid squares). Normalised percentage positive expression shown. Mann–Whitney two-tailed t-test, median and interquartile ranges are indicated (***P = 0·0002). (E) Correlation between normalised percentage Siglec-15+ and CD33+ populations from 10 patients with AML. Pearson’s correlation: r = 0·9354, P < 0·0001, two tailed test. (F) Geometric mean of fluorescence intensity (gMFI) values of A9E8 binding normalised against isotype binding for PBMCs expressing cell-surface Siglec-15 from 12 patients with AML (open circles) and 12 healthy donors (solid squares). Mann–Whitney two-tailed t-test, median and interquartile ranges are indicated (***P = 0·0002). Credit: DOI: 10.1111/bjh.17496

Researchers have made a huge leap forward in finding a targeted therapy for acute myeloid leukemia.

The innovative 'magic bullet' technique uses specific antibody-targeting technology that would reduce the need for that can be arduous, invasive and require long hospital admissions.

Acute leukemia (AML) generally affects older people with around three thousand people diagnosed per year in the UK alone. Current treatments can involve the use of bone marrow transplantation which can be painful, arduous and can sometimes bring with it unpleasant side effects.

The researchers found that in AML, there is a high concentration of a molecule named Siglec-15 found on the surface of the diseased cell. The team identified a molecule that could bind to Siglec-15, piggyback into the cell and take with it a toxin that could potentially kill off the diseased cell, thereby eradicating the disease without damaging healthy .

Published in the British Journal of Haematology, and funded by the Biotechnology and Biological Sciences Research Council (BBSRC), the study was led by Dr. Huan Cao, Research Fellow at the University of Aberdeen, alongside colleagues at Cambridge University where much of the work was carried out.

Dr. Cao explains: "We are looking to find a cure for leukemia by using targeted antibody therapy known as 'magic bullets.' For this we needed to identify a cancer specific target and make an antibody against it.

"We found that in acute myeloid leukemia, Siglec-15 is highly expressed compared to and set out to find a way to use this over-expression to our advantage. By identifying a molecule that binds to Siglec-15, we unlock the potential to attach a toxin to it which can then be carried into the cell and ultimately destroy it.

"In this way then it is possible that anti-Siglec-15 might be used as a "magic bullet" to treat AML cells by introducing toxins into the diseased cells. "

Although magic bullets have been used in some types of cancer, this is the first time it has been explored in AML.

Dr. Cao adds: "Acute myeloid leukemia is a big killer especially for the elderly population. The "magic bullet" can be very effective with minimal side effects which means it could be hugely beneficial to an already vulnerable population.

"Although still in the experimental phase, if all goes well—there is potential that this may be used clinically as a treatment for patients within the next three to five years."

More information: Huan Cao et al, Sialic acid‐binding immunoglobulin‐like lectin (Sigelac)‐15 is a rapidly internalised cell‐surface antigen expressed by acute myeloid leukaemia cells, British Journal of Haematology (2021). DOI: 10.1111/bjh.17496

Journal information: British Journal of Haematology

Citation: 'Magic bullet' found in fight against leukemia (2021, November 10) retrieved 23 September 2023 from https://medicalxpress.com/news/2021-11-magic-bullet-leukemia.html
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