Molecule That Can Treat Cancer Patients


The researchers at Tel Aviv and the University of Lisbon identified a molecule that can successfully treat multiple types of cancers. Moreover, it is an effective and accessible alternative to an antibody. The results of the study have been published in Journal for ImmunoTherapy of Cancer.

Professor Satchi-Fainaro, Kadar Family Award Recipient said,

In 2018, the Nobel Prize in Medicine was awarded to James Allison and Tasuku Honjo for their contribution to the study of immunotherapy, the treatment of cancer through activation of the immune system.

He further added,

Honjo discovered that immune cells called T cells express the protein PD-1 which disables the T-cells’ own activity when it binds to the protein PD-L1 expressed in cancer cells. In fact, the interaction between PD-1 and PD-L1 allows cancer cells to paralyze the T cells, preventing them from attacking the cancer cells. Honjo developed antibodies that neutralize either PD-1 or PD-L1, thereby releasing the T cells to fight cancer effectively.

The antibodies, which will fight against PD-1/PD-L1 proteins have been approved for clinical use. Furthermore, immunotherapy will also improve patient outcomes significantly. The side effects will be minimal, which is not the case considering chemotherapy. However, the production of the antibodies is costly and not available to all patients. Additionally, the treatment does not affect every part of solid tumours because the antibodies are very large. They are unable to access and penetrate the less exposed areas.

Smaller Antibody Alternatives

However, researchers are now using bioinformatic and data analysis tools to look for smaller alternatives to these antibodies. Professor Satchi-Fainaro said,

Post-doctoral researcher Dr Rita Acúrcio started with thousands of molecular structures, and by using computer-aided drug design (CADD) models and databases, we narrowed down the list of candidates until we reached the best structure.

He further added that in the second stage they confirmed the effectiveness of the small molecules on tumour growth. It helped in inhibiting PD-L1 in animals, which were engineered to have T cells like humans. Moreover, the new molecule has advantages in comparison with antibody treatment.

First of all, the cost: since the antibody is a biological rather than a synthetic molecule, it requires a complex infrastructure and considerable funds to produce, costing about $200,000 per year per patient. In contrast, we have already synthesized the small molecule with simple equipment, in a short time and at a fraction of the cost. Another advantage of the small molecule is that patients will probably be able to take it at home, orally, without the need for IV administration in the hospital.

Other than the accessibilty, experiments showed that the small molecules improve immune cell activations inside the tumour mass.

Professor Stachi-Fainaro explained,

The surface area of a solid tumour is heterogeneous.

If there are fewer blood vessels in a particular area of the tumour, the antibody will not be able to get inside. The small molecule, on the other hand, diffuses and is therefore not entirely dependent on the tumour’s blood vessels or on its hyperpermeability. I believe that in the future, the small molecule will be commercially available and will make immunotherapy affordable for cancer patients.


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