Gene-modified cell therapy for the treatment of cancer and other diseases is a rapidly growing area of clinical research. The therapeutic use of engineered cells has necessitated the development of novel lab tests for assessing patient safety and efficacy. We’ll explore how unique applications of PCR and flow cytometry can be used to provide critical and complementary data that is needed to bring new life-saving treatment options to patients.
Cell therapy involves employing human cells to treat genetic diseases, cancer and infectious diseases; the manipulated material can either be from the patient’s own cells (autologous) or from a donor (allogeneic). Gene-modified cell therapies involve engineering the donor cells using customised lentiviral or retroviral vectors that have been altered to remove most of the viral genes. The altered viral vectors allow a functioning human gene to be integrated into the genome of the donor cells.
What is CAR-T?
A common gene-modified cell therapy is chimeric antigen receptor T cell therapy (CAR-T), a progressive new immune cell therapy used to treat cancer. CAR-T cells are engineered ex vivo to express a functioning receptor that recognises tumour antigens, resulting in the attack and destruction of the tumour cells. Following the gene modification and manufacturing process, the CAR-T cells are infused into the patient. Several CAR-T therapies have been approved for the treatment of haematological malignancies.
Biomarkers of CAR-T Response
Since its development, CAR-T therapy has transformed the treatment landscape for haematological malignancies. As with any novel treatment, CAR-T therapy isn’t without its challenges. Not all patients respond to treatment. Moreover, the duration of response to CAR-T therapy can be variable. Various factors could be potential predictors of response and the duration of remission such as the patient’s age, tumour burden and CAR-T dose. More recently the cellular kinetics of the CAR-T cells during the first 3-6 months have been shown to be promising potential biomarkers of response. As a “living drug”, CAR-T cells exhibit the phases of distribution, expansion, contraction, and persistence following administration. Measuring the cellular kinetics of a “living drug” requires novel assay designs.