Cristina G. Lucio Madrid

Madrid

Updated Wednesday, February 14, 2024-20:00

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They are called

'dagger' cells

, from their English acronym -

STAb

-, a striking name that describes their way of acting. It is explained by Luis Álvarez Vallina, 'father' of this treatment that is intended to improve immunotherapy against cancer. "In some way what these cells do is

deliver daggers

, they get other lymphocytes that are nearby to arm themselves against the tumor and fight it, which is why we named them that."

Although still in laboratory trials, this treatment is showing very good prospects for advancing the fight against cancer. The latest of this evidence is published this week in the journal

Science Translational Medicine

.

The work, led by the H12O-CNIO Cancer Immunotherapy Clinical Research Unit directed by Vallina, shows that in experimental models this new immunotherapy is

more effective than CAR-T against multiple myeloma.

What is multiple myeloma

This type of cancer is the second most common hematological tumor in adults and one of the pathologies for which the use of CAR-T is authorized, a type of immunotherapy that makes it possible to provide the body's 'defenses' with external weapons against the cancer. To carry out this therapy, the patient's own lymphocytes are extracted and genetically modified to identify and attack the tumor before infusing them back into the body.

To know more

Oncology.

Antoni Ribas: "In the not distant future the CAR-T will be manufactured in a box"

  • Editor: CARMEN FERNÁNDEZ Barcelona

Antoni Ribas: "In the not distant future the CAR-T will be manufactured in a box"

Advanced therapies.

They design a "super T lymphocyte" that multiplies its potential to attack incurable cancers by a hundred

  • Editor: SONIA MORENO Madrid

They design a "super T lymphocyte" that multiplies its potential to attack incurable cancers by a hundred

It is a very effective treatment that, however,

does not prevent relapses

in a considerable percentage of patients.

According to Vallina, STAb cells provide several advantages over conventional CAR-T cells, which would allow them to offer an alternative to patients with recurrent myeloma and propose a new approach.

Both cells are produced in a similar way and, in the case of myeloma, they recognize the same antigen, called

BCMA,

which is only present in tumor cells. But, unlike CAR-T, STAb-T cells have the ability to

recruit other lymphocytes and arm them

to enhance the fight against cancer.

What are the differences between CAR-T and

STAb-T

?

"CAR-T cells only activate those cells that express the chimeric receptor on their surface. STAb-T cells, on the other hand, produce a biospecific antibody that allows activation bridges to be established not only with the cells that produce it but with other lymphocytes T that may be in proximity. Therefore, the therapy

has a very notable amplification effect

," explains Vallina.

Furthermore, STAb-Ts are also not held back by an obstacle that stops CAR-Ts: the presence of the BCMA antigen in soluble form, a phenomenon that occurs when there is a high tumor burden. "It is something that greatly affects CAR-T but we have seen that the same does not happen with STAb-T cells," clarifies the researcher who, in the work that is now published, has compared the effects of conventional CAR-T immunotherapy. against multiple myeloma with dagger cell-based immunotherapy.

Another advantage is that STAb-T cells generate

immunological memory

. "We have seen that cells can persist and that is very relevant for them to ultimately have clinical efficacy," comments Vallina, who summarizes that "these three reasons make the therapy allow control in laboratory models in a much more effective way and at much higher doses." lower than CAR-T the disease.

Two years for human trials

The team, in which researchers from the Josep Carreras Leukemia Research Institute, the Hospital Clínic of Barcelona and the Universities of Salamanca and Complutense of Madrid have also participated, wants to start human trials as soon as possible, a process that It will last at least two or three years, depending on the requirements established by the regulatory agencies.

"It is a very exciting time for cancer immunotherapy. All the evolutions of CAR therapies and the advances that we will see in the coming years will change the paradigms, the ways we have to deal with many tumors," says the researcher who emphasizes that "

In Spain, top-level research can be done

if scientists have the appropriate resources. We have done this thanks to the support of many foundations, both public and private, and the collaboration of multiple research groups in our country and we hope that it will pay off as soon as possible. possible in a benefit for all patients in a sustainable way.

Puñal cells are already being tested in trials with patients with

B-cell acute lymphoblastic leukemia

and there are different preclinical approaches to evaluate their use in other types of hematological diseases and even solid tumors.

"The STAb-T cell strategy is novel and, in this

in vitro model,

appears to have certain advantages in relation to the CAR-T lymphocytes themselves on myeloma tumor cell lines and in the animal model used, based on greater cytotoxicity and a reduction in potential resistance mechanisms. However, since STAb-T cells have not yet been used in patients, it is not yet possible to assess their potential implications in the treatment of myeloma or how they might fit into the current therapeutic landscape. "Toxicity data are also needed," recalls Fermín Sánchez-Guijo, head of the Hematology Service at the University Hospital of Salamanca, in statements to the Science Media Center (SMC).

"The main limitations of the work are that the in vitro

studies

have been carried out with tumor cell lines and in an immunosuppressed animal model, as the authors themselves have highlighted," he adds.

Also speaking to SMC, Ignacio Melero, highlights the novelty of the strategy and the fact that "the effect against malignant cells seems very powerful in cell cultures and in immunodeficient mice grafted with human multiple myeloma cells", although, As in the case of Sánchez-Guijo, remember that "both treatments with CAR-T and bispecific

T cell engager

antibodies raise problems of acute toxicity in patients due to hyperinflammatory cytokine release syndromes. If clinical trials are developed, this aspect must be considered with special care and regulate the production of the bispecific antibody so that it is only expressed when it works by recognizing the antigen or incorporating other security measures.