The history of Immunotherapy as a means to engage the immune system for treating cancer goes back to the late 19th century and William B. Coley, MD. In 1961 T cells were identified to develop in the thymus gland by Immunologist Jacques Miller. 1973 saw Memorial Sloan Kettering using allogenic bone marrow transplantation as a means to boost a patient’s blood cells post-chemotherapy. They noted that the transplanted T cells began reducing the number of cancer cells in the recipient. In the mid-1980’s a novel therapy using tumor-infiltrating lymphocytes were extracted from a tumor, expanded in-vivo, and reinfused back into the patient with promising results. Noteworthy progress was made in the 1990’s with the manipulation of T cells (making them enhanced cancer fighters), the creation of First-Gen CARs, and finally their use in cancer patients. It was not until 2017 that the first CARs were approved for use by the FDA, these therapies were for the treatment of relapsed, refractory (r/r) acute lymphoblastic leukemia in children and young adults.
Acute lymphoblastic leukemia (ALL) can occur at any age and is generally a disease of children and young adults. Numerous studies show that ALL accounts for approximately 25% of cancers in children less than 15 years of age and about 19% of malignancies in adolescents between 15-19 years of age. While there have been advances in the treatment of pediatric ALL (mainly to avoid chemotherapy resistance) newer therapies have been needed. With the development of CARs that target the B cell protein CD19, significant improvements in remission rates have been achieved (between 81-90%). When this document was written, only one commercially available CAR T therapy was approved for use in pediatric patients.
CAR T-cell therapy is commonly called “personalized medicine” or a “personalized cellular therapeutic” as the patients’ own T cells are used in the CAR T-cell treatment. The T cells from the patient’s own blood are isolated, genetically re-engineered to include a chimeric antigen receptor, cultured in the lab, and then shipped back to the physician treating the patient. A “lymphodepletion chemotherapy” is administered prior to the infusion of the engineered CAR T-cells. When the treatment works as intended, the CAR T-cells become part of the patients’ normal blood supply, begin expanding (growing in numbers) and attacking the cancer-causing B-cells. Over a period of time the CAR T-cells become exhausted as they eradicate the cancer cells (stop expanding in numbers), this is called persistence.
This newer therapy is welcomed as an advancement in the treatment of pediatric leukemias. Historically, the treatment for leukemia has been primarily dependent on chemotherapy agents. With overwhelming side effects and the indiscriminate targeting of both healthy and cancer cells by chemotherapy agents, CAR T-cell therapy is a targeted treatment that spares normal, healthy cells in the body. A noteworthy side effect of CAR T-cell therapy is known as cytokine release syndrome (CRS) or a cytokine storm (CS). CRS is caused by the patients’ immune system activating when it begins attacking the tumor cells. The first couple of weeks are critical for monitoring the patient for signs or symptoms of a CRS or CS episode. Physicians and the medical staff are trained in what to watch for and will monitor the patient closely during this time. There are specialized treatment options to help mitigate CRS and CS, if necessary.
When it comes to CAR T-cell therapy for pediatric patients, several factors need to be considered during laboratory testing to ensure optimal treatment outcomes. These considerations include the unique biological characteristics of pediatric patients, the specific types of cancers prevalent in this population, and the potential impact of prior treatments. While CAR T-cell therapy offers promising outcomes, rigorous laboratory testing is crucial to ensure its safety and efficacy. Eurofins Viracor, a leading diagnostic laboratory, plays a pivotal role in providing comprehensive laboratory testing services to support CAR T-cell therapy for pediatric patients.
Eurofins Viracor offers a portfolio of advanced diagnostic tests ranging from comprehensive immunophenotyping of T-cells, organ function testing, Cytokine assays and the ExPeCT™ CAR T-cell anti-CD19 assay that measures the expansion and persistence of immunologically modified T-cells. By utilizing advanced technologies and methodologies, Viracor assists clinicians in patient selection, treatment monitoring, and the early detection of potential complications. This collaborative approach between Eurofins Viracor and healthcare providers contributes to the successful implementation of CAR T-cell therapy for pediatric patients, ultimately improving the outcomes and quality of life for children with cancer.