A group of researchers from the Centro Nacional de Investigaciones Oncológicas (CNIO), the Hospital del Mar Research Institute (HMRIB) and the Instituto de Investigación del Hospital 12 de Octubre (i+12) has designed a new strategy that makes it possible to modulate, through a drug, the activity of the latest-generation STAb-T type cellular therapy against hematological cancers and solid tumors.
As the CNIO points out, this drug acts as a kind of chemical switch capable of turning the cellular therapy on and off, which makes it easier to adjust the intensity of the treatment and, therefore, reduce the risk of high toxicity. The work, disclosed in the journal 'Advanced Science', has evaluated this approach both 'in vitro' and in murine models.
Cell therapies represent the current leading form of personalized cancer treatment, since they are generated from the patient's own T lymphocytes, which are modified in the laboratory and then reinfused. This is intended to achieve a more precise intervention with fewer adverse effects.
Although these therapies are already applied in clinical practice for certain blood cancers, the number of patients who can benefit remains limited. In this setting, the objective of the study is to broaden the range of tumors to which these strategies can be directed and, at the same time, minimize their complications.
The team headed by Luis Álvarez-Vallina has found that the drug not only triggers the modified T lymphocytes, but also allows their activity to be adjusted according to the administered dose. The authors emphasize that this is the first time this type of control has been achieved in STAb-T therapies.
A "dagger cells" therapy with a chemical switch
Like the rest of cell therapies, STAb-T, known as "dagger cells" therapy, is based on modifying the patient's lymphocytes. The particular feature of this approach is that the modified T lymphocytes release bispecific antibodies, capable of selectively activating the patient's immune system.
"In STAb-T immunotherapy, modified T cells produce bispecific antibodies, which form bridges between the T cell and the tumor cell. This bridge further enhances the ability of T cells to identify and destroy the tumor cell," Álvarez-Vallina explained.
The work has managed for modified T lymphocytes to generate separately the different components of these bispecific antibodies. "And only when the patient receives the drug does the active bispecific antibody assemble," the researcher has detailed, emphasizing that this mechanism makes it possible to turn the system on or off and even adjust its power and the time during which it remains active.
"The drug acts as a chemical switch. The modified T lymphocytes only activate and assemble the two antibody modules in the presence of the drug, triggering the immune response against the tumor," Susana Luengo-Arias, first author of the study, has detailed.
This control is especially relevant in solid tumors, since many of the therapeutic targets are also found in healthy tissues. The therapy has been tested 'in vitro' and in mice, both in models of hematological cancers directed against the protein CD19 and in solid tumors that use the protein EGFR as a target.
This approach, which still needs to undergo new safety studies and clinical trials in patients before being applied in humans, opens the way to safer, modifiable, and tailored cellular immunotherapies for each case.