New therapeutic agents tighten up immune response against cancer

José Pichel Andrés/DICYT The research team led by Jesús San Miguel, professor of Hematology at the Universidad de Salamanca and head of the Department of Hematology at the Hospital Universitario de Salamanca, works hand in hand with another team from the Centro de Investigación Médica Aplicada (CIMA), a center for applied medical research in Pamplona (Spain), conducting studies on new therapeutic agents to enhance patients’ immune response against cancer. Specifically, their chief objective is to bring this type of clinical research to hematological malignancies working with the team led by Ignacio Melero Bermejo, researcher at CIMA.

"We are developing strategies to convince the immune system that it has to display its ability to kill cells and tissues against tumors, using a series of tools performing with immune system cells to increase its antitumor activity," as DiCYT was told by the scientist at CIMA, who talked about his work at a research conference for experts at the Centro de Investigación del Cáncer (CIC) de Salamanca, a cancer research center in Spain, in February 2013.

So far, almost all tests performed in this area are related to solid tumors, but scientists believe that in hematologic malignancies this new therapeutic approach must be at least "equally effective". Consequently, Ignacio Melero contacted Jesús San Miguel to try different drug families related to immune response.

New therapeutic tools are based on immunostimulatory monoclonal antibodies, that is, antibodies interacting with immune system receptors. "If we invoke a car metaphor, these receptors act like brakes and accelerators. We want antibodies to spoil brake response, so the car’s performance would be more intense, or to intensely hit accelerators," he states.

The beginning trials in hematological tumor patients will take at least a year, as we were told by Ignacio Melero, who has a long collaboration history with Salamanca, as he had previously worked with Alberto Orfao’s team monitoring antitumor immune responses because of the ICC scientist "enormous prestige" in flow cytometry.

In this area, the CIMA is also looking for strategies aimed to transfer cells from the immune system, activated to induce endogenous immune responses or to get a more powerful response. Other target strategies are based on the insertion of engineered communication elements into the immune system to make them more powerful and able to induce an effective immune response against tumors.

Trials have been performed in animal models and in patients. "We have developed a wide range of clinical trials in patients with advanced malignancies in order to prove, working with the pharmaceutical industry or on our own, their antitumor effect studying their mechanisms of action,” he states.

Remarkable Progress

Actually, his group has a drug approved by the FDA to fight metastatic melanoma, a monoclonal antibody targeted against CTLA-4 (Ipilimumab marketed as Yerboy), that may also have other indications. Moreover, other antibodies are at clinical development advanced stages (phase II and phase III) progressing with "very good prospects".

The experience of his research team has scientific milestones. "We have worked on one specific monoclonal antibody immunostimulant, CD137 molecule, one of the molecules acting as an accelerator. We found it very powerful in animal models and we are to perform a pioneering test worldwide, working with other five centers,” he explains.

The CIMA has also taken part in early clinical trials of molecules called PD-1 and PDL-1 (their action mechanism still fields many questions). "We are trying to understand why they are very effective in some patients and so inefficient in some others," he states.