Senescent cells as vaccines against cancer

Cancer cells have a series of features that allow the immune system to identify and attack them. However, these same cells create an environment that blocks immune cells and protects the tumour. This means that immune cells cannot reach the cancer cells to remove them. The scientific community has been working for years to increase the effectiveness of the immune system against cancer by using vaccines based on dead tumour cells.

Scientists at IRB Barcelona, led by ICREA researcher Dr. Manuel Serrano, and Dr. Federico Pietrocola, now at the Karolinska Institutet, in Sweden, have studied how inducing senescence in cancer cells improves the effectiveness of the immune response to a greater degree than the dead cancer cells. After vaccinating healthy mice with senescent cancer cells and then stimulating the formation of tumours, the researchers observed that the animals did not develop cancer or that the number that do is significantly reduced. They also analysed the efficacy of vaccination in animals that had already developed tumours. In this setting, although the results were more moderate due to the protective barrier of the tumour, improvements were also observed.

"Our results indicate that senescent cells are a preferred option when it comes to stimulating the immune system against cancer, and they pave the way to considering vaccination with these cells as a possible therapy," explains Dr. Serrano, head of the Cellular Plasticity and Disease lab at IRB Barcelona.

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Drug Encapsulation System Selectively Targets Senescent Cells

A team headed by Manuel Serrano at IRB Barcelona has designed a drug encapsulation system that selectively targets senescent cellsThe study paves the way for therapeutic approaches to eliminate senescent cells in many diseases, such as pulmonary fibrosis and cancer.

Senescent cells are damaged cells that do not perform their normal roles anymore but that are not dead –hence they are commonly known as zombi cells. These cells interfere with the functioning of the tissue in which they accumulate. Senescence is a cell program that is triggered by many types of damage and senescent cells are present in many diseases. They accumulate in diverse types of tissues during aging, thus contributing to the progressive deterioration associated to aging. Eliminating these zombi cells is one of the challenges facing science today.

In the Cellular Plasticity and Disease lab headed by the ICREA researcher Manuel Serrano at the Institute for Research in Biomedicine (IRB Barcelona) and supported by “la Caixa” Banking Foundation, the researchers devise strategies to eliminate senescent cells.  In a study published in EMBO Molecular Medicine, they present a proof of principle of a drug delivery system with selectivity for tissues that harbour senescent cells.

In collaboration with a team headed by Ramón Martínez-Máñez at the Universidad Politécnica de Valencia, the IRB Barcelona scientists have exploited a particular hallmark of senescent cells in order to design a delivery system that specifically targets them. They have demonstrated its efficacy in cells in vitro and in two experimental mouse models, namely pulmonary fibrosis and cancer. These diseases are characterized by the presence of damaged cells, and in the case of cancer this is particularly true after treatment with chemotherapy.

The figure shows two views, frontal and lateral, of the image obtained by CT of the lungs of a mouse with fibrosis (grey areas) before and after receiving nano-therapy directed at senescent cells

In these models, the senescent cells take up the carrier more efficiently than other cells and once inside the cell the casing of the carrier degrades to release the drug cargo. When the nano-vehicles contained cytotoxic compounds, the senescent cells were killed and this resulted in therapeutic improvements in mice with pulmonary fibrosis or with cancer.

This nano-carrier may pave the way for new therapeutic approaches for serious conditions, such as pulmonary fibrosis or to eliminate chemotherapy-induced senescent cells, explains Manuel Serrano. Another outcome of this study is that these nano-carriers could be used for diagnostic tests of senescence as they can transport a fluorescent compound or marker.