Biologists from Switzerland and Germany have developed a new immunotherapy that does not require knowledge of the antigenic composition of the tumor, paving the way for new cancer treatments that are the first of their kind.
The Medical Express website reported on the new study that dendritic cells (DCs) work at the forefront of the immune system. They can effectively capture antigens, such as fragments of viruses, bacteria and transformed cancer cells. Dendritic cells can also direct other immune cells against those agents that invade the body. This process often leads to the activation of a second type of immune cell, namely killer T cells (known by several abbreviations as cytotoxic T lymphocyte, CTL, T-killer cell, cytolytic T cell, CD8+ T-cell or killer T cell), which can Eliminate infected or abnormally mutated cells. Thus, dendritic cells play an important role in regulating immunity against pathogens and cancer cells.
Unfortunately, tumors often erect barriers against the body’s immune system, allowing cancer to grow out of control. This setback, known as “immunosuppression,” may involve suppression of dendritic cells and paralyzing their ability to present tumor antigens to killer T cells (CD8 + T cells).
Addressing limitations of conventional vaccines
Over the past few decades, researchers have worked to overcome tumor-induced “immunosuppression” through various strategies, collectively called “immunotherapies,” some of which are approved treatments that are effective in patients with certain types of cancer.
One approach is to generate dendritic cells from blood mononuclear cells (a type of immune white blood cell) of a patient with cancer, expose them in the laboratory to material derived from a tumor biopsy (called the antigen loading step) and then reintroduce them into the patient’s body. This procedure, often referred to as dendritic cell vaccination, greatly enhances the presentation of tumor antigens to killer T cells.
However, dendritic cell vaccines have given mixed results in clinical trials. One potential limitation of these vaccines is the use of mononuclear cell-derived dendritic cells. These cells lack some essential properties of naturally occurring dendritic cells, such as type 1 dendritic cells (cDC1), which play a crucial role in activating killer T cells.
Another potential drawback of this strategy is its reliance on the antigen loading step, which uses pre-selected antigens that may not represent the full spectrum of relevant antigens present in cancer cells. However, addressing these shortcomings of traditional dendritic cell vaccines could enhance their therapeutic efficacy.
A team of scientists led by Michele De Palma, assistant professor in the School of Life Sciences and director of the Agora Center for Cancer Research in Switzerland, has developed engineered dendritic cells with the ability to transform into type 1 dendritic cells (cDC1) and stimulate anti-tumor immunity when transferred into mice. tumors, without the need for an antigen loading step. The study was published in the journal Nature Cancer.
“Our strategy does not use the mononuclear cell-derived dendritic cells used in previous studies, but relies on a population of cells, called DC progenitors (DCPs) that we can produce in the laboratory from readily available sources, such as blood and bone marrow,” Di Palma explains.
Go beyond results
When engineered to express two immune-stimulating molecules (IL-12 and FLT3L), the DCP cell can initiate effective anti-tumor immune responses in various cancer models, surpassing results achieved with other conventional dendritic cell constructs.
“Remarkably, the engineered DCP cells worked, in the absence of antigen loading, meaning they could be effective against a wide range of human cancers, regardless of the antigens they express,” according to the study.
The ability of engineered DCP cells to broadly engage multiple components of the immune system, not limited to killer T cells, may explain their efficacy. “A very promising result was the ability of DCP cells to unleash the efficacy of chimeric receptor T cells (CAR-T) in eliminating brain tumors in mice,” says Professor Denis Migliorini, Head of the Department of Neuro-Oncology at the University of Geneva and one of the study’s authors.
CAR-T cells are another class of engineered immune cells already approved to treat some tumors, but their effectiveness in brain cancer has been limited so far. “We are committed to combining DCPs with CAR-T cells in patients with incurable brain cancer,” Migliorini adds.
“Our pre-clinical results require further development and testing before moving to clinical application,” cautions De Palma.
DCPs can be easily obtained from human blood, facilitating the translation of preclinical findings into potential cancer immunotherapy.
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