Cohorts and Clinical Trials

Cohorts and clinical trials play a fundamental role in the medical research landscape, serving as the cornerstone for validating the effectiveness and safety of new treatments.

Within the realm of oncology, the focus on hematological malignancies, particularly in the context of allogeneic stem cell transplantation and other immune therapies, is of paramount importance. The rigorous investigation and analysis of these treatments through carefully designed clinical trials are pivotal for the translation of innovative therapies from the research bench to bedside application. This process ensures that new treatments can be safely and effectively integrated into clinical practice, offering hope to patients with conditions that were previously deemed intractable.

A notable aspect of this research involves the development of unique allogeneic stem cell transplantation cohorts that undergo alpha-beta (ab) T cell depletion. This methodological approach is designed to facilitate a more focused study on the roles and therapeutic potentials of gamma delta (γδ) T cells and natural killer (NK) cells. By selectively depleting abT cells, researchers can create an immunological environment that allows for the enhanced activity and assessment of γδT cells and NK cells, which are believed to contribute to the graft-versus-leukemia effect without causing graft-versus-host disease. This approach not only enables a deeper understanding of these cells' roles in combating hematological malignancies but also offers a platform with potentially fewer long-term side effects compared to traditional treatments. Such innovative cohort designs are critical for advancing our knowledge and application of immune therapies in clinical settings. 

In addition to the focus on allogeneic stem cell transplantation and the study of γδ T cells and NK cells, the research group is actively involved in conducting clinical trials for chimeric antigen receptor T (CAR-T) cell therapies and αβT cells engineered with a specific γδT cell receptor (TEGs). Engineered immune cell therapy represents a groundbreaking approach in cancer treatment, where patients' T cells are genetically engineered to express CARs or T cell receptors (TCRs) that specifically target tumor-associated antigens, thereby enhancing the immune system's ability to recognize and destroy cancer cells. The ongoing trials with engineered immune cells aim to assess the efficacy and safety of these therapies in treating various hematological malignancies, with the goal of refining engineered immune cell designs and treatment protocols to maximize patient outcomes.

Together, the efforts in conducting clinical trials for CAR-T cell therapies and TEGs, alongside the development of unique cohorts for studying the roles of γδ T cells and NK cells, underscore the comprehensive and innovative approach to combating hematological malignancies. By advancing these cutting-edge therapies through rigorous clinical testing, the research group is at the forefront of transforming cancer treatment, moving promising new therapies from the laboratory into clinical practice and ultimately improving patient care and outcomes.

Most recent clinical studies

·        TARGET study (RCT) (NL64877.041.18). Accrual finished.

·        TEG001 study (Phase 1) (NL6357), principal investigator. Recruiting.

References

·      Translating γδT cells and their receptors into cancer cell therapies. Nature Reviews Drug Discovery  2020

·      αβT cell graft depletion for allogeneic HSCT in adults with hematological malignancies. Blood Advances 2021