February 26, 2024

Small Molecule Developed That Makes Immunotherapy Available to All Cancer Patients

In other words, we have established a molecule that can hinder PD-1/ PD-L1 binding and advise the immune system that it requires to attack the cancer.
I think that in the future, the small molecule will be commercially available and will make immunotherapy affordable for cancer patients.”

Molecular docking of ligand candidates on PD-L1 protein structure. Credit: Dr. Rita Acúrcio
The clinical use of antibodies against the PD-1/ PD-L1 proteins has actually currently been licensed, and they are considered holding the greatest capacity for the fight against cancer. This immunotherapy can drastically improve client outcomes, without the severe adverse effects that accompany treatments such as chemotherapy.
However, the antibodies are pricey to produce, and therefore not offered to all clients. The treatment does not impact all parts of the solid tumors due to the fact that the antibodies are too big to penetrate and reach less accessible and less exposed areas of the tumor. Now, researchers at Tel Aviv University and the University of Lisbon have actually utilized bioinformatic and data analysis tools to find a smaller, smarter alternative to these antibodies.
From delegated right: Prof. Helena Florindo, Prof. Ronit Satchi-Fainaro, Dr. Rita Acúrcio, Prof. Rita Guedes. Credit: Eric Sultan & & University of Lisbon
” Post-doctoral scientist Dr. Rita Acúrcio started with countless molecular structures, and by utilizing computer-aided drug style (CADD) models and databases, we narrowed down the list of prospects till we reached the very best structure,” says Prof. Satchi-Fainaro. “In the second phase, we validated that the small particle controls tumor development as efficiently as the antibodies– it inhibits PD-L1 in animals engineered to have human T cells. Simply put, we have developed a particle that can hinder PD-1/ PD-L1 binding and advise the body immune system that it requires to assault the cancer.
” Moreover, the brand-new molecule has some significant benefits over the antibody treatment. Of all, the expense: because the antibody is a biological rather than an artificial molecule, it requires a complicated facilities and considerable funds to produce, costing about $200,000 per year per client.
In addition to availability considerations, experiments reveal that the little particle enhances the activation of immune cells inside the solid growth mass.
“If there are fewer blood vessels in a specific location of the growth, the antibody will not be able to get within. I think that in the future, the small particle will be commercially offered and will make immunotherapy budget friendly for cancer clients.”
Reference: “Therapeutic targeting of PD-1/ PD-L1 blockade by unique small-molecule inhibitors hires cytotoxic T cells into strong growth microenvironment” by Rita C. Acúrcio, Sabina Pozzi, Barbara Carreira, Marta Pojo, Nuria Gómez-Cebrián, Sandra Casimiro, Adelaide Fernandes, Andreia Barateiro, Vitor Farricha, Joaquim Brito, Ana Paula Leandro, Jorge A R Salvador, Luís Graça, Leonor Puchades-Carrasco, Luís Costa, Ronit Satchi-Fainaro, Rita C. Guedes and Helena F. Florindo, 21 July 2022, Journal for ImmunoTherapy of Cancer.DOI: 10.1136/ jitc-2022-004695.
This work was supported by Fundação para a Ciência e a Tecnologia, Ministério da Ciência, Tecnologia e Ensino Superior (FCT-MCTES), by The Israeli Ministry of Health under the frame of EuroNanoMed-II, “La Caixa” Foundation, Liga Portuguesa Contra o Cancro, the ERC, The Israel Science Foundation, The Melanoma Research Alliance, the Israel Cancer Research Fund (ICRF) Professorship award and the Morris Kahn Foundation..

Scientist identified and synthesized a small particle that might be a more reliable and available option to an antibody that is successfully used to treat a series of cancers.
A small molecule that might be a more available and efficient option to an antibody that is successfully utilized to treat a variety of cancers has been identified and synthesized by scientists at Tel Aviv University and the University of Lisbon. The outcomes of the research study were published in the Journal for ImmunoTherapy of Cancer.
Behind the groundbreaking development is a worldwide team of researchers. They were led by Prof. Ronit Sachi-Fainaro, Head of the Center for Cancer Biology Research and Head of the Laboratory for Cancer Research and Nanomedicine at the Sackler Faculty of Medicine, Tel Aviv University, and Prof. Helena Florindo and Prof. Rita Guedes from the Research Institute for Medicines at the Faculty of Pharmacy, University of Lisbon.
” In 2018, the Nobel Prize in Medicine was granted to James Allison and Tasuku Honjo for their contribution to the study of immunotherapy, the treatment of cancer through activation of the immune system,” says Prof. Satchi-Fainaro, a 2020 Kadar Family Award recipient. “Honjo discovered that immune cells called T cells express the protein PD-1 that disables the T-cells own activity when it binds to the protein PD-L1 revealed in cancer cells. The interaction between PD-1 and PD-L1 enables cancer cells to disable the T cells, avoiding them from attacking the cancer cells. Honjo established antibodies that reduce the effects of either PD-1 or PD-L1, therefore releasing the T cells to fight cancer efficiently.”

“Honjo discovered that immune cells called T cells express the protein PD-1 that disables the T-cells own activity when it binds to the protein PD-L1 expressed in cancer cells. The interaction in between PD-1 and PD-L1 enables cancer cells to paralyze the T cells, preventing them from attacking the cancer cells. Honjo established antibodies that neutralize either PD-1 or PD-L1, therefore launching the T cells to fight cancer effectively.”