Next-generation CAR-T therapies for pediatric sarcomas: Biotechnological advances show promising results

Although sarcomas account for only a small percentage of all malignant tumors, their diagnosis and treatment remain a challenge. Biotechnology is opening new therapeutic avenues, especially in the development of advanced cellular immunotherapies tailored to these rare tumors.

Sarcomas are malignant tumors that originate in the connective tissue of soft parts of the body, excluding bones and cartilage. According to the Spanish Association Against Cancer (AECC), this group includes tissues that provide structural support or fill spaces in the body: adipose, muscle, tendon, blood vessels, nerves, and deep layers of the skin.

Sarcomas are considered rare diseases, which is why July 13 is marked as International Sarcoma Awareness Day—a key date to raise visibility and awareness about these mesenchymal-origin tumors.

"Within CIBERONC, we are developing an ambitious project focused on creating advanced cellular immunotherapies for pediatric sarcomas, particularly Ewing sarcoma," explains Enrique de Álava, Group Leader at the CIBER Cancer Area (CIBERONC), a consortium partner of AseBio.

This project brings together leading translational biomedical research groups with the aim of generating new CAR-T cell therapy strategies tailored to the biological characteristics of these rare, poor-prognosis tumors. "The research combines molecular biology, preclinical models, genetic engineering, and immunotherapy, with a strong translational focus," adds the researcher.

Sarcoma in numbers

The World Health Organization (WHO) has identified more than 150 types of sarcomas. In Spain, nearly 2,600 new cases are diagnosed each year. Although their incidence is low—about 1% of malignant tumors in adults and 13-15% in children—they account for approximately 2% of cancer-related deaths.

According to data from the Spanish Federation for Rare Diseases, around 40% of diagnoses are delayed or incorrect, and one in four patients initially receives treatment for a different condition.

Biotechnology for Personalized Therapies

Thanks to current biotechnological tools, it is now possible to precisely analyze the protein and gene expression profiles in both tumors and healthy tissues. This enables the identification of potential therapeutic targets that are both tumor-specific and safe.

In the case of sarcoma, new proteins have been found on the surface of tumor cells, which may serve as targets for highly selective immunotherapies. “These findings are serving as a foundation to design personalized cell therapies that recognize and attack only tumor cells, minimizing side effects,” explains De Álava.

The team is currently validating these therapies in preclinical models and working toward their clinical translation. This includes strategies to overcome barriers posed by the tumor microenvironment, which often limits the effectiveness of immunotherapies in solid tumors. These CAR-T therapies are based on novel tumor targets identified through advanced transcriptomic and proteomic analyses.

Technical, Regulatory, and Economic Barriers

Clinical translation, funding, and regulation are among the key challenges for treatments targeting rare diseases such as sarcomas. Transforming an experimental therapy into an available option for patients requires navigating a complex process involving preclinical validation, GMP-compliant production, ethical and regulatory approvals, and the appropriate hospital infrastructure.

Despite these challenges, CIBERONC is making efforts to shorten development timelines, as demonstrated by the recent exceptional compassionate use of one of these cell therapies in a pediatric patient with Ewing sarcoma who had no other treatment options.

“Collaboration is key,” says De Álava. “Our project involves clinical centers, academic groups, and biotech companies, combining expertise in molecular diagnostics, immunotherapy, preclinical models, and technology transfer.” This synergy allows for resource sharing, faster knowledge generation, and progress toward more personalized medicine.

One of the consortium’s most recent milestones, as a partner of AseBio, has been the development of a new generation of CAR-T therapies for pediatric sarcomas. These have shown promising results in preclinical models and have already led to a compassionate use request. The advance was jointly led by Dr. Enrique de Álava’s group (Institute of Biomedicine of Seville, IBiS-HUVR) and Dr. Pablo Menéndez’s group (Josep Carreras Institute, led by Dr. Anna Bigas), within the framework of CIBERONC.

This translationally driven project has been made possible thanks to the support of the Ministry of Science and Innovation through the 2022 Strategic Lines Collaboration Call, co-funded by Spain’s Recovery, Transformation and Resilience Plan and the European Union’s NextGenerationEU funds.