Treating Breast Cancer in Mice

 

Chinese team says vaccine shows promise in treating breast cancer in mice



Chinese scientists have developed a nanovaccine from tumour cell membranes that they say has shown promise in treating an aggressive form of breast cancer in mice.

The nanovaccine is designed to boost the immune response of B cells – an abundant white blood cell found in tumours – which is known to have anti-tumour effects through multiple mechanisms.

“Inoculation with tumour cell membrane-derived vaccines is a promising strategy to activate B cells, yet their efficiency is limited due to lack of co-stimulatory molecules,” the researchers wrote in a paper published in peer-reviewed journal Advanced Materials last month.

To overcome this challenge, the team from the Shanghai Institute of Materia Medica, Chinese Academy of Sciences designed a tumour cell membrane-derived vaccine that also has components to stimulate an immune response.

When tested on mice with triple-negative breast cancer – an invasive form that cannot be treated with hormone therapy – the nanovaccine achieved a tumour inhibition rate of 89.3 per cent, according to the paper.

Nanovaccines derived from cell membranes are an emerging type of vaccine. They are made from naturally derived tumour cell membranes that are extracted and made into nanoparticles while retaining antigens that can be used to trigger an immune response.

This can allow for more personalised, effective and targeted cancer vaccines. They can even be extracted from a patient’s own tumour cells, though challenges remain – including the potential for adverse side effects.

Globally, a woman is diagnosed with breast cancer every 14 seconds. Some 2.3 million women were diagnosed with breast cancer in 2022, and 670,000 died from the disease that year, according to the Breast Cancer Research Foundation in New York.

Triple-negative breast cancer – where the cancer cells lack receptors for oestrogen or progesterone – is an invasive form with a high risk of recurrence.

More tumour-associated antigens are expressed with this form of breast cancer, and the tumours also see a higher infiltration of B and T cells – another form of white blood cell. That makes it a promising target for a tumour antigen vaccine.

To make a vaccine that activates both B and T cells, cell membranes from the tumour cells were extracted. Two immune enhancers were then coupled onto a structure on the membranes.

These were CpG, an immune-stimulative short DNA molecule, and an anti-CD40 antibody which recognises a protein found on antigen-presenting cells.

This was made into a nanovaccine called CM-CpG-aCD40. It accumulates in lymph nodes after injection and is then picked up by antigen-presenting cells. Tumour antigens on the nanovaccine bind to B cell receptors, providing a stimulation signal for B cell activation, according to the team.

They said the vaccine delivers tumour-specific antigens, co-stimulatory molecules and components that enhance the immune response. That means it has multiple ways to activate an immune response.

The tumour inhibition rate of the nanovaccine was further improved to 95.4 per cent when combined with an antibody for the programmed death ligand (PD-L1) – a protein that is known as an immune “brake”.

The researchers said the nanovaccine was found to take advantage of multiple functions of B cells within anti-tumour immunity when suppressing tumour progression in mice, indicating the significant potential of B cell-targeted tumour vaccines.

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