New Drug Combo Could Help Immune Cells Target and Destroy Cancer Cells

Researchers have identified a promising new drug combination that could significantly help the immune system target cancer cells and kill them.

The study published in Cell, describes a treatment that works by combining an intravenous dosage of a well known anti-nausea drug, prochlorperazine (called Stemetil in Australia), with existing cancer treatments.

University of Queensland (UQ) scientist Associate Professor Fiona Simpson, who led the exhaustive research project, said it could lead to new treatments for some cancers.

Dr Simpson has spent the past decade working on the research project, a tribute to her mother who she lost to cancer in 1999.

"The anti-nausea drug works by changing the surface of the tumour cells so that existing cancer drugs which target tumours are better able to interact with the immune system," Dr Simpson said.

"The result is that cancer cells become sitting targets that can no longer escape the immune system.

"We observed a process we haven't seen before and which increased the 'natural killer' immune cells' ability to attach to, and kill the cancer. It is almost as if the killer cells become zipped to the tumour cells."

The treatment can be combined with and improve the effectiveness of existing cancer drugs like cetuximab, trastuzumab and avelumab and was studied on tumours from head and neck, breast and metastatic colorectal cancers in mice, as well as five patients with head and neck cancer.

"These heroic patients volunteered for a 'no benefit trial', consenting to have a tumour biopsy followed by a 20-minute intravenous transfusion of Stemetil, and then another biopsy," Dr Simpson said.

"We were able to show that the Stemetil altered the tumour cell surface in these patients."

Following the initial findings, the researchers combined Stemetil with an anti-cancer antibody drug resulting in the disappearance of all the tumours from ten mice with head and neck cancer.

Dr Simpson was curious to see what would happen if they re-introduced the same cancer back into the mice four weeks later.

"Amazingly, their cancer was rapidly eliminated - as if the new combination, in addition to being more effective, was also able to teach the immune system how to better recognise cancer cells," Dr Simpson said.

"The mice developed a long-term immunity to the cancer they initially had."

The Fiona Simpson Cancer Research group has been working with expert immunologists including UQ's Dr James Wells to translate the research findings to patient treatments.

"Our long-term vision is to use this approach to not only clear a patient's cancer in the immediate term, but to prevent their cancer coming back in the future by establishing protective 'immune memory'," Dr Wells said.

Dr Simpson's team is now completing a safety trial of the combination of Stemetil and cetuximab in head and neck cancer, triple-negative breast cancer and adenoid cystic carcinoma patients at the Princess Alexandra Hospital.

The collaboration involved researchers and doctors from UQ's Diamantina Institute and Institute for Molecular Bioscience, The Princess Alexandra Hospital, Children's Medical Research Institute, The University of Newcastle and The University of Sydney.

The University of Queensland's technology transfer company UniQuest will seek to identify commercialisation opportunities.

Reference: Chew, et al. (2020) Endocytosis Inhibition in Humans to Improve Responses to ADCC-Mediating Antibodies. Cell. DOI: https://doi.org/10.1016/j.cell.2020.02.019 

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