There is a goal – there will be a result
An international team of researchers from the Cancer Center of the University of North Carolina (Chapel Hill, USA) in collaboration with colleagues from the Research Institute Fondazione Istituto di Ricerca e Cura a Carattere Scientifico (Milan, Italy) conducted a number of preclinical studies on cell culture and mice and described a new point of application of immune cells modified for the treatment of glioblastoma.
The target was a molecule of chondroitin sulfate proteoglycan 4 (chondroitin sulfate proteoglycan 4, CSPG4), which is found in large quantities in cancer cells.
This study is part of a research program launched at the University of North Carolina Cancer Center to develop personalized immunotherapy using chimeric antigen receptor T-lymphocytes (CAR T-cell therapy).
CAR T therapy consists in taking the patient's immune cells and gene modification to give them the ability to recognize and destroy cancer cells. The authors of the study chose CSPG4 molecules as a target for T-lymphocytes, located in large numbers on the cell surface of 67% of glioblastoma samples.
Critically important when choosing a target for immune cells is its presence in tumor cells and its absence in healthy ones. CSPG4 is just such an antigen.
In addition, CSPG4 is found in a group of so-called cancer-initiating, or cancer stem cells. The destruction of the latter guarantees a complete cure, minimizing the risks of relapse or metastasis.
In experiments using CSPG4-targeted T-lymphocytes, it was possible to control tumor growth. In the culture of glioblastoma cells, with the introduction of modified T-lymphocytes, tumor growth stopped, while the presence of unchanged T-lymphocytes did not affect the progression of glioblastoma in any way. The same results were obtained in a study on mouse models of glioblastoma.
In addition, scientists have discovered a mechanism that makes it possible to increase the effectiveness of the investigated method of potential therapy by increasing the expression of CSPG4 in tumor cells. In studies on mice, the introduction of tumor necrosis factor (TNF-alpha) led to an increase in the production of CSPG4 in tumor cells.
The authors write that the results of an in vitro and in vivo study with CSPG4-targeted T-lymphocytes can become the basis for the development of a drug for both combined and monotherapy of an almost incurable disease to date – glioblastoma.
During the study, cancer cells had some immunosuppressive effect, which suppressed the activity of modified T-lymphocytes. This problem has yet to be solved in further research.
Article by S. Pellagatta et al. Constitutional and TNFa-inducible expression of chondroitin sulfate proteoglycan 4 in glioblastoma and neurospheres: Implications for CAR-T cell therapy is published in the journal Science Translational Medicine.
Aminat Adzhieva, portal "Eternal Youth" http://vechnayamolodost.ru based on UNC at Chapel Hill School of Medicine: Researchers identify molecular target for brain cancer, develop immunotherapy approach to attack it.