Multiple myeloma is the second most common blood cancer in adults. One of the major advances in its treatment in recent years has been CAR-T cell immunotherapy, in which a patient’s own T lymphocytes (white blood cells) are genetically modified so that they can specifically recognize and destroy tumor cells.
However, CAR-T therapy is a complex, time-consuming, and very costly cell-based treatment. T cells must first be collected from the patient, then modified and expanded in the laboratory before being reinfused into the body with the ability to target cancer cells.
The group led by Luis Álvarez-Vallina at the CNIO has just received funding from the Deutsche José Carreras Leukämie Stiftung for a project aimed at modifying T cells directly within the patient’s body. This approach could significantly reduce manufacturing costs and shorten treatment times, ultimately allowing more patients to benefit from these therapies.
The project, called LIVE-STAb (In vivo generation of engineered T cells secreting T-cell engager antibodies with targeted lentiviral vectors), is co-led by Christian J. Buchholz, from the Paul-Ehrlich-Institut in Germany.
The researchers will employ so-called STAb-T cells, which can be considered an evolution of CAR-T cells. In both cases, the engineered cells recognize the same antigen found exclusively on tumor cells, enabling them to selectively target and attack cancer cells.
STAb-T cells, however, a field in which Álvarez-Vallina’s group has particular expertise, offer substantial advantages. Most notably, they are able to recruit unmodified T cells already present in the body, enlisting them in the fight against cancer cells and thereby amplifying the therapeutic effect.
BCMA-specific STAb-T cells (red) recognize and attack myeloma cells (blue). Credit: Anaïs Jiménez-Reinoso (Cancer Immunotherapy Clinical Research Unit H12O-CNIO) and Manuel Pérez and Isabel Peset (Confocal Microscopy Unit) / CNIO.
As Álvarez-Vallina explains, “We will develop a pioneering strategy to generate BCMA-targeted STAb-T cells [BCMA is an antigen found exclusively on multiple myeloma cells] directly within the patient, eliminating the need for ex vivo cell manufacturing. The project will evaluate the feasibility, efficacy, and safety of this innovative approach.”
The goal of LIVE-STAb is “to establish a new paradigm for genetically engineered T-cell therapies, making advanced immunotherapies faster, more accessible, and more scalable for patients with multiple myeloma and other types of cancer.”
Image: Luis Álvarez-Vallina, head of the HMarBCN -CNIO Cancer Immunotherapy Clinical Research Unit, at CNIO. / Laura M. Lombardía. CNIO
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