BiTE®, a little-known immunotherapy with an innovative mechanism of action against cancer

With the increase in life expectancy in developed societies, there has also been an increase in certain diseases associated with aging. Cancer is the most common of all, which makes it already considered the biggest social and health problem in the world. As reported by the Spanish Association Against Cancer (AECC), it is expected that one in two men, and one in three women, will suffer from it throughout their lives.

Hence the importance of the scientific community not ceasing its efforts to find, if not a cure, at least treatments that make the disease chronic, allowing cancer patients to live with relative normality and quality of life.

For some years now, immunotherapies have been revolutionizing the fight against cancer. Among the different existing typologies, those developed with BiTE® technology (English abbreviation for bi-specific T-cell engagerwhich would be literally translated into Spanish as ‘bispecific T cell activator’).

The operation of BiTE® technology is based on acting as a bridge that connects the T cells of the immune system with tumor cells, allowing their elimination, with minimal impact on healthy tissues.

Developed by Peter Kufer, a scientist at the biotechnology company Amgen, its mechanism of action is characterized by using bispecific monoclonal antibodies designed to simultaneously bind to two targets. In simpler words, BiTE® works as a smart bridge that connects two types of cells. On the one hand, they connect to T cells, which are like the “soldiers” of the immune system responsible for attacking threats. On the other hand, they identify and latch onto cancer cells, directly destroying them. All this is possible because in both types of cells there are special surface “tags” through which the BiTE® can identify the two types of cells between which it will act as an “intelligent bridge”. That is, it is as if they put the soldiers right in front of the enemy, guiding them so that they can accomplish their mission more effectively.

They thus differ from other immunotherapies that use monoclonal antibodies directed at a single target or more complex molecules, such as genetically modified T cells (CAR-T), which require additional cellular engineering of the blood that has to be carried out outside the patient’s body. .

As explained by Dr. José Luis Fuster, head of the Pediatric Oncology and Hematology Service at the Virgen de la Arrixaca University Clinical Hospital in Murcia, “T cells are lymphocytes (the natural cells of the immune system) capable of fighting and eliminating infectious agents. and also tumor cells. BiTE® technology designs molecules, which we call bispecific antibodies, that are capable of fixing or binding to two targets at the same time, one of them on the tumor cell and another on an effector cell or T lymphocyte of the patient. “In this way, the interaction between the immune system and tumor cells is favored, thus promoting the elimination of the latter.”

The operation of the “bispecific” mechanism that allows these molecules to attack tumor cells is very simple. In the words of Dr. Ribera, “BiTE® molecules are small molecules. So by attaching on the one hand to the tumor cell and on the other to the T lymphocyte, they allow the lymphocyte to come into direct contact with the tumor cell and release substances such as granzymes and perforins, which allow said cell to be destroyed. That is, the secret is that the contact between the T lymphocyte and the tumor cell is so close that it allows direct destruction.”

The company Amgen has been a pioneer in the development of this technology and was the first to get a BiTe® therapy approved by the European Medicines Agency

Dr. Josep Maria Ribera, senior consultant of the Clinical Hematology Service of the Institut Català d’Oncologia at the Germans Trias i Pujol Hospital and head of the ALL group of the PETHEMA group highlights that, “for now, this technology has been used in the treatment of hematological cancers such as acute lymphoblastic leukemia and aggressive lymphomas, but in theory it could be applied to other cancers.”

A new horizon

The company Amgen has been a pioneer in the development of this technology and was the first to get a BiTe® therapy approved by the European Medicines Agency in 2015. But its scientific advances have gone even further with the improvement of the technology and the introduction of HLE BiTE® (Half-Life Extended BiTE®), which, thanks to their optimized structure, manage to remain active in the body for longer, reducing the need for constant infusions and significantly improving the quality of patients’ lives.

In addition to offering new hope to all those who are fighting cancer, BiTE® HLEs open a horizon of possibilities by allowing the immune system not only to attack current tumor cells, but also to develop an immunological memory capable of preventing relapses in the future. In this way, it is not only possible to effectively treat the disease, but also to strengthen the body’s natural defenses to combat it in the long term.

“These advances have demonstrated great effectiveness in the management of complicated patients, such as those who suffer one or several relapses of certain malignant hematological diseases, such as leukemia.”

Dr. Fuster,head of the Pediatric Oncology and Hematology Service of the Virgen de la Arrixaca University Clinical Hospital in Murcia

For Dr. Fuster, these advances represent “an alternative therapeutic approach to the classic tools of cancer treatment that for decades have been represented by chemotherapy, radiotherapy and surgery. It is therefore free of many of the undesirable effects of treatment with these classic tools.”

But the most important thing, in his opinion, is that “they have demonstrated great effectiveness in the management of complicated patients, such as those who suffer one or several relapses of certain malignant hematological diseases, such as leukemia. In some cases, the administration of bispecific monoclonal antibodies in combination with other agents has transformed the prognosis of certain pathologies and has also made it possible to reduce the intensity of other treatment strategies that are administered in parallel or sequentially.”

A key technology in leukemias

BiTE® technology can change the near future of the treatment of some types of cancer. As Dr. Fuster highlights, “in recent years, pediatricians dedicated to oncohematology have witnessed a transformation in the therapeutic approach to the most common malignant disease in childhood, acute lymphoblastic leukemia.”

In his opinion, “in the short term, the use of bispecific monoclonal antibodies will be generalized and applied to all patients who do not respond adequately to conventional treatment or who suffer a relapse and, in the medium term, the use of this type of drugs “It will also be applied in first-line treatment.”

As Dr. Ribera points out, “collaboration between academic research and directly supported by pharmaceutical companies is and will continue to be key to the development of immuno-oncology.”