Breakthrough Antibody Method: How UC San Diego Fights Treatment-Resistant Tumours

Researchers at the University of California at San Diego have developed a new approach that tackled a key driver of treatment resistance and metastasis -- a protein called integrin Alpha-v-beta3.

The new method fights the protein by taking advantage of the tumour's own immune landscape.

"In a breakthrough from UC San Diego School of Medicine, researchers have developed an antibody optimisation mechanism that could help tackle treatment-resistant tumours," Mazumdar-Shaw said in a post on social media platform X.

"It can potentially boost current immunotherapies and offer new hope for patients," she added.

Integrin Alpha-v-beta3 remains absent in normal tissues but is enriched in aggressive tumours.

Previous attempts to target the protein with antibody therapies worked by activating a specific type of cell in the immune system called natural killer cells.

However, this approach failed to significantly improve patient survival in clinical trials, potentially because the tumours didn't have enough natural killer cells to mount a strong immune response.

In the new study, published in the journal Molecular Cancer Therapeutics, the researchers engineered a new anti-Alpha-v-beta3 antibody that activates macrophages, a type of immune cell that is already abundant in advanced Alpha-v-beta3 tumours.

With the new approach, the researchers were able to trigger powerful anti-tumour responses in both patient tumour samples and in mouse models.

It also led to increased tumour cell death and reduced tumour growth.

However, the anti-tumour effect was entirely dependent on macrophages; when macrophages were depleted, the therapy lost its effectiveness, while depletion of natural killer cells had no impact, the researchers said.

"The antibody optimisation strategy could serve as a blueprint for treating other treatment-resistant tumours, potentially improving a wide range of existing immunotherapies and offering new hope for patients with advanced cancers," said the researchers from the varsity's School of Medicine.

- IANS