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Research succeeds in developing antibodies that recognize human tumor cells

2020-12-01T02:07:15.975Z


The work, with Spanish participation, is a step in the search for cancer vaccinesThe strategy used to develop a vaccine against the coronavirus, getting the immune system itself to identify and fight the disease from its inception, also applies to cancer. The Faculty of Chemistry of the University of Seville has joined this front, which, in collaboration with the universities of La Rioja and Zaragoza, the CIC-BioGUNE, the CSIC and also European researchers (Lisbon, Cambridge a


The strategy used to develop a vaccine against the coronavirus, getting the immune system itself to identify and fight the disease from its inception, also applies to cancer.

The Faculty of Chemistry of the University of Seville has joined this front, which, in collaboration with the universities of La Rioja and Zaragoza, the CIC-BioGUNE, the CSIC and also European researchers (Lisbon, Cambridge and Copenhagen) and Japan ( Hokkaido), has developed antibodies that recognize overexpressed glycoprotein fragments in human tumor cells.

The vaccine proposal is based on an amino acid sequence linked to a carbohydrate portion (glycopeide) that acts against the Tn antigen, one of the most common in tumors.

Faced with this substance Tn, which should generate the body's immune response, according to Carmen Ortiz Mellet, lead author of the study, published in

Chemical Science

, “natural antibodies are not very effective due to immunotolerance problems: being present in a very low proportion also in healthy cells, the organism tends to consider it as its own in tumor cells and the immune response is low ”.

Ortiz Mellet's research has overcome this limitation.

“Not only this, but we have also seen that a significantly greater number of antibodies are produced of those with long-term memory, those of the IgG type, than those that originate with an identical vaccine, but in which the antigen is the natural one ”.

“At the moment, tests on two different types of breast cancer cells indicate that recognition exceeds 85%.

This is very relevant.

Although the term cancer really refers to many different diseases, these data, which are still very preliminary, suggest that the number of patients that could benefit from a vaccine of this type is high, "he says.

This line of research, the generation of antibodies against a non-natural analog of the antigen, is unique and, according to the scientist, from the Department of Organic Chemistry of the University of Seville, "opens new opportunities in the design of vaccines against cancer" .

“The basic principle is to mimic the carbohydrate part of this antigen present in tumor cells, so that it is different enough to stimulate the immune system more powerfully, but similar enough so that the antibodies that are they generate recognize the natural Tn antigen and thus eliminate tumor cells in the patient ”, explains the researcher.

Another of the innovations of this work has been the use of imino sugars (carbohydrate analogs) that "not only reproduce the structure of the carbohydrate present in the Tn antigen, but also its chemistry."

"This is a unique characteristic of this research, which allows the synthesis of the vaccine and, in addition, provides it with additional stability, contributing to its higher efficacy," says Ortiz Mellet.

Also, the University of Arizona has presented to the Society for Cancer Immunotherapy a clinical trial with "promising" results in its first phase, according to Julie E. Bauman, director of the institution's cancer center.

The North American study has been developed with 10 patients with head and neck cancer.

Five of them experienced a clinical response to the personalized vaccine and two patients had a complete response and have no detectable signs of the disease.

“The data is preliminary and the sample size is small, but it is promising.

A phase I trial is about safety first and foremost, and we now know that this treatment is safe and tolerable, ”says Bauman, who will expand the trial.

Another front against metastasis

Research on a possible cancer vaccine is not the only open front.

A work by Manuel Sarmiento Soto, Marie Curie researcher from the Group of Cell Death Mechanisms in Neurodegenerative Diseases at the University of Seville, in collaboration with the University of Oxford, has managed to study an immediate consequence of breast cancer metastasis in cells more abundant in the brain (astrocytes) and identify an inhibitor that allows the recovery of neurovascular functions

“Metastasis is like throwing a stone into a pond;

it is difficult to control the consequences of the waves it generates ”.

With this simile, Sarmiento Soto explains how the metastatic process (the spread of the tumor from its origin to another part of the body) generates a storm in other vital cells from the first moment.

When cancer spreads to the brain, the resident cells are seriously imbalanced in their functions.

Sarmiento has focused on the effects of metastasis on astrocytes, which are key to neuronal activity, since they are the most abundant cells in the brain and are responsible for regulating blood flow in an organ that, although it accounts for 2% of our body weight, demands 20% of the oxygen we assimilate.

Without a balanced functioning of this, cerebrovascular function is significantly compromised and the door is opened to serious sequelae.

With the mediation of the STAT3 protein, key in the activation of astrocytes, a molecular alteration occurs during metastasis in all affected cells.

"It not only displaces astrocytes, but also causes them to lose control of the blood supply," Sarmiento explains.

"And this effect occurs from the early stages of tumor spread," he adds.

Research has identified that the molecule called WP1066 acts as an inhibitor of the effects on astrocytes, the most abundant cells in the brain, and allows them to regain control over blood flow

The key to the study, published in

Cancer Research

, in addition to the use of technology that has made it possible to investigate the effects of STAT3 on brain cells at micrometric levels and in real time, has been the identification of a molecule, called WP1066, which acts as inhibitory effects on astrocytes and allows them to regain control over blood flow in the brain.

Research has focused on the effects of breast cancer metastasis, but Sarmiento believes it is "potentially" applicable to other types of tumors.

The supply of this molecule has no adverse effects described to date and research shows that it lessens the effects of metastasis and slows its progression.

“It not only acts on astrocytes but also on other cells that are over-activated by STAT3.

In some cases they are diseases where survival is counted for months, so it is a great advance ”, adds the researcher.

This same inhibitor has already been used in current clinical trials, a circumstance that, together with its easy administration and its ability to enter the brain, allows the leap to clinical studies on patients.

STAT 3 is the acronym for so-called signal transducers and activators of transcription.

These transducers, which transform hormonal action into enzyme activity and have essential functions in the healthy body, are associated with increased activities of one or more proteins and are often activated in tumor cells.

Genetics

Another line of study against cancer, according to a study published in

Nature Communications

by the Genomics and Oncology Research group (GENYO), of the University of Granada, the Junta de Andalucía and Pfizer, it is related to the mobile genetic elements called LINE-1 or L1.

“98% of the genome is made up of mobile genetic elements: DNA sequences that have the ability to jump from one place to another.

Fortunately for us, almost all of them have accumulated mutations that prevent them from mobilizing, and there is only one family capable of making the proteins it needs to jump: the L1 elements ”, explains Pablo Tristán, GENYO researcher and first author of this work.

"Our objective was to study if any of the microRNAs could control L1 jumps and, therefore, if alterations in microRNA levels - something common in cancer - could contribute to the increase in L1 jumps observed in tumors," adds Sara Rodríguez. Heras, Ramón y Cajal researcher from the Department of Biochemistry and Molecular Biology II of the University of Granada.

Researchers have discovered a new role for the let-7 family of microRNAs as tumor suppressors by acting as guardians of the genome and maintaining its integrity in the face of mutagenic activity of mobile elements.

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Source: elparis

All news articles on 2020-12-01

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