Completed Cancer Cells, Biochemistry & Physiology

Development of peptide-drug conjugates for the treatment of Chronic Myelomonocytic Leukaemia (CMML)

In plain English

AI plain-English summary

A new class of drug delivers a highly toxic compound directly into cancerous blood cells, sparing healthy tissue, in experiments with cells and animals. This matters because chronic myelomonocytic leukaemia (CMML) has no generally effective treatment. Half of patients die within 15–20 months of diagnosis. Standard chemotherapy fails because it cannot distinguish between cancerous and healthy cells, or it cannot reach the bone marrow cells that drive relapse. The researchers have already shown that a prototype of this drug selectively kills CMML cells in a test tube and maintains that activity and selectivity in animal models. In this project, they will refine the prototype to ensure it has all the properties needed for human testing. If successful, the work will generate the data required to move one of these compounds into final toxicity tests and then clinical trials in patients. The potential impact is direct: a targeted therapy for a blood cancer that currently offers patients little hope. If the drug works in humans, it could become the first effective treatment for the majority of CMML patients, changing a prognosis that is now measured in months.

View original technical description
Chronic Myelomonocytic Leukaemia (CMML) is a type of blood cancer for which is no generally effective treatment. For the majority of people diagnosed with CMML the prognosis is dismal, with 50% of patients dying within 15-20 months of diagnosis. Chemotherapy approaches in CMML frequently fail due to a lack of selectivity for the cancerous cells relative to the rest of the patient's body, or lack of activity against the cancerous cells in the bone marrow that cause the disease to recur. We are seeking to address this shortfall by developing a new class of drug that selectively targets and kills the cancerous cells through the patient's body, with little or no impact on healthy cell types. We will achieve this by attaching a highly toxic compound to a protein that is taken up only by the type of cells that have become cancerous in patients with CMML. We have demonstrated that a prototype of these drugs can selectively target and kill CMML cells in a test tube and that this activity and selectivity is maintained in animal experiments, which are needed to model the complex requirements of treating a patient with CMML. In this project we will conduct further studies to make as sure as possible that these compounds will be useful for treating CMML, whist also developing these prototypes to ensure they have all the required properties for testing in patients. If successful this will give us all the information we need to take one of these drugs into final toxicity tests and then clinical trials in CMML patients.

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Researchers

Alan Dickson (Co-Investigator)Daniel Scotcher (Co-Investigator)Daniel Wiseman (Co-Investigator)Douglas Dyer (Co-Investigator)John Grainger (Co-Investigator)Katherine Finegan (Co-Investigator)Kiran Batta (Co-Investigator)Sam Butterworth (Principal Investigator)Tim Somervaille (Co-Investigator)

Related Research

Grants with similar aims, by meaning.

Synthesis of PROTAC-Antibody Conjugate for Application in Acute Myeloid Leukemia Therapy
Feasibility Study for a Novel Drug Conjugate Treatment for Pancreatic Cancer
Design, synthesis and evaluation of peptide-drug conjugates that recruit and reprogram innate immune cells in cancer.
Development of a novel, targeted cytotoxic treatment for breast cancer
Developing Novel Bispecific Antibody-Drug Conjugates to Treat Leukaemia

Original classification

Research Grant

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