For a very long time, cancer treatment has relied on the three pillars of surgery, chemotherapy, and radiation therapy. However, in recent years, the emergence of immunotherapy has added a whole new set of unique tools that enhance the body’s own immune system to fight cancer.

Cell therapy treatment uses body cells to treat the patient. The cells are manipulated or edited to change certain biological characteristics before being transferred to the patient. In immunotherapy, manipulation of key cells in the immune system enables the patient’s own defence to recognize and fight the cancer.

Cell therapy can be divided into stem cell- and non–stem cell-based. The transfer of cells could either originate from the patient (autologous cells) or from a donor (allogeneic cells). Stem cells are a type of unspecialized, self-renewable cells prepped to differentiate into any cell type. Non–stem cell-based therapies use different types of cells, such as immune cells, skin cells, connective tissue cells, liver cells and pancreatic islet cells. The scope of this article, however, is the blood cells used in the manufacture of advanced therapies.

The immune cells are a blood component commonly called white blood cells and they fight infections and participate in the immune response. The white blood cells can be further distinguished into lymphocytes and monocytes. The two main types of lymphocytes are T lymphocytes (T cells) and B lymphocytes (B cells), but there is also another subtype called Natural Killer (NK) cells.

Dendritic cells belong to a different kind of white blood cells called monocytes. When harmful foreign particles enter the body, the dendritic cells notify other immune cells to come to the site of the infection and destroy the invader. T-, B-, NK- and dendritic cells are all used in the manufacture of cell-based advanced therapies.

Chimeric antigen receptor (CAR) T cell therapy, is a type of personalised therapy where T cells taken from the patient’s blood are genetically modified to express chimeric antigen receptors (CARs) designed to identify and bind to proteins expressed on cancer cells. Large numbers of the CAR T cells are then grown in the laboratory and re-infused back into the patient where they bind to an antigen on the cancer cells and kill them. CAR T-cell therapy is typically used after other types of treatment have been tried treat certain blood cancers such as some types of lymphomas and leukaemia’s, as well as multiple myeloma.

Cancer cells have an inherent mechanism to escape detection and destruction by T cells by downregulating of certain proteins that would normally be recognised by the immune defence. The development of CARs circumvents this as they are engineered to function independently of the regular system for recognition. They can therefore bind to and eliminate potentially harmful cells that can cause infection, cancer, and other maladies.

Although CAR T cells are showing good results in blood cancer, success has not yet translated into solid tumour indications. The T cell receptor (TCR) is a molecule on the surface of T cells that specifically recognizes intruders (so called non-self proteins) and mediates immune responses. Binding to the intruder protein, the TCR triggers a chain reaction that ultimately leads to the death of the intruder.

TCR therapy employs genetically modified T cells that are directed against specific tumour markers. A biopsy from the tumour is used to screen for the expression of a specific protein for the T cells to target. TCR-T cells are then engineered to recognise the tumour protein in order to kill tumour cells. The advantage is that TCR T cells can recognise not only proteins on the cell surface of the cancer cell but proteins inside the cell (intracellular antigens) which allows TCR-T cells to recognize a wider spectrum of target antigens.

Both CAR-T and TCR techniques are based on a similar manufacturing process. TCR therapies are still in clinical trials and are currently not approved for clinical use.

Dendritic cells are immunological sentinels, playing a prominent role in the immune defence, always attentive to sense and monitor the presence of dangerous foreign material in the body. These cells can regulate the immediate defence by their ability to detect a wide variety of danger signals but are also specialised to process and present foreign proteins to the adaptive immune response, which basically means that they educate T cells on what to attack.

When used in advanced therapies, dendritic cells are extracted from the patient’s blood and engineered to recognise and present proteins related to tumours and can therefore be used to train T cells to target and kill cancer cells.

Natural killer (NK) cells belongs to the body’s first-line defence. In contrast from T or B cells, NK cells respond to invading threats without prior recognition, they instead act in an instant by killing the intruder. NK cells can distinguish between healthy and ‘stressed’ cells, i.e., virus infected cells or cancer cells. Tumours can create a favourable environment by downregulating markers the immune response normally would recognise and thereby divide and grow without interference. But as NK cells are able to recognise cells lacking these specific markers (= stressed cells), they pick up that something is wrong. They then start sending out signals making the tumour environment more inflammatory and thereby recruiting more immune cells to the site ready to defend the body against the tumour.

The most recent progress of the use of NK cells in immunotherapy is to combine the chimeric antigen receptor with instead of with T cells, creating CAR-NK cell therapy. NK cells are suggested superior due to its unique features, possibly with less side effects compared to T cells and without the need to be the patient’s own cells, therefore NK cell therapies have an ‘Off the shelf’ potential.

ancer is a complex disease. Incredibly diverse, manifesting in many different organs and behaving very differently. Cancer is also both self and non-self as tumours arise from cells in our own body but are abnormal and not supposed to be there. The immune system is also highly multifaceted, and the evolving understanding of its complexity has resulted in different therapeutic approaches to direct the body’s own response in advanced and more personalised therapies.

At NDA, we have extensive experience working with cell-based products and genetically modified cells. If you are looking to advance your cell therapy, connect with our team using the form below.