What is Cellular Therapy?

Dr. CHAN Chi Fung, Godfrey

Honorary Consultant in Paediatrics

Specialist in Paediatric Haematology & Oncology

Recently, the term “cellular therapy” has been quoted frequently in the media. What does it mean?

In simple terms, it is the utilisation of human cells to treat certain diseases. The oldest form of cellular therapy is blood transfusion, i.e. either red blood cells, platelets or white blood cells from donors are infused into the recipients to replace the deficit or overcome infection. 

Then the more complicated form of cellular therapy is haematopoietic stem cell transplantation (HSCT or the old term “bone marrow transplantation”). The infused haematopoietic stem cells can either salvage a failed marrow (such as aplastic anemia or after megadose chemotherapy) or exert immune cytotoxic action as in allogeneic (from other donor) setting. The latest advancement in HSCT is to make use of either in-vivo or in-vitro methods to deplete unwanted immune cells so we can select HLA half-matched person as donors (i.e. parents).

Other forms of cellular therapy include the ex-vivo expanded immune cells for treatment of cancers (such as dendritic cells, cytokine induced killer cells, etc.) or somatic stem cells for regenerative purposes. The ex-vivo expanded autologous immune cells, though still being used in several countries, have limited evidence to support their application.  

However, the current hot topic is not about the above methods. It is referring to some bio-engineered immune cells known as chimeric antigen receptor T cells (CAR-T). This form of treatment is based on our knowledge of molecular genetics as to how lymphocytes can recognise a target. In natural conditions, upon antigen exposure, naive lymphocytes will turn into memory cells by undergoing a genetic sequence change in their immunoglobulin receptor gene (immunoglobulin gene rearrangement). Each rearranged gene sequence is specific to a particular antigen or target. By knowing a particular rearranged gene sequence for our targeted antigen, we can now replicate this gene sequence and insert it to the T lymphocytes through various techniques (either viral vector or physical methods). Then the T lymphocytes will be “educated” and can identify the specific antigen target to exert their killing action.

Though it sounds tedious, the process can be processed in an automated fashion which is suitable for mass production under GMP regulation. CAR-T cells have been successfully applied clinically to refractory leukaemia and lymphoma and have been approved in many countries as a form of rescue treatment. But it is expensive, and its uses have thus been strictly monitored by expert panels in many countries. The efficacy of CAR-T cells in solid tumors also remains to be verified, as the immunosuppressive cancer microenvironment often hinders its action. Other than T cells, CAR-Natural Killer cells have also been currently applied in clinical trial.