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ESTRO 2016: Radiation and L19-IL2 Immunotherapy Combination Shows Activity in Preclinical Models

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Key Points

  • L19-IL2 is a combination of an antibody that targets tumor blood vessels and cytokines.
  • Researchers found not only that the mice were tumor-free following treatment, but also that when reinjected with cancer cells 150 days after cure, they did not form new tumors.
  • There was also an increase in the number of cells with an immunologic memory. 

Radiation therapy not only targets and destroys cancer cells, but also helps to activate the immune system against their future proliferation. However, this immune response is often not strong enough to be able to completely eradicate tumors, and even when it is, its effect is limited to the area that has been irradiated. Now, however, research presented at the European Society for Radiotherapy & Oncology (ESTRO) 35 Conference on May 1 (Abstract OC-0234) has shown that the addition of an immune system–strengthening compound can extend the radiation therapy–induced immune response against the tumor sites, and that this response even has an effect on tumors outside the radiation field.

Nicolle Rekers, MSc, from the Department of Radiation Oncology, Maastricht University Medical Centre, Maastricht, The Netherlands, described how a combination of radiation therapy and L19-IL2, an immunotherapy agent, can increase significantly the immune response when given to mice with primary colorectal tumors. L19-IL2 is a combination of an antibody that targets the tumor blood vessels and cytokines.

Study Findings

The researchers found not only that the mice were tumor-free following treatment, but also that when reinjected with cancer cells 150 days after cure, they did not form new tumors. There was also an increase in the number of cells with an immunologic memory.

“Radiation therapy damages the tumor, creating a sort of tumor-specific vaccine,” said Ms. Rekers. “It feeds the immune system and ensures that it notices that something is wrong. What is unique about our latest experiments is that we have been able to create a so-called abscopal effect, where a localized radiation treatment has also had an effect on other tumor sites outside this radiation field.”

The lifespan of mice is quite short—about 2 years—so 150 days is a relatively long time. “Of course, these mice are models of human disease and can never be 100% comparable with a patient, but the fact that the cured mice never formed new tumors, compared with a 100% tumor formation in untreated mice of the same age, is significant. We will know more after analyzing results from the phase I/II clinical study in human patients that we started recently,” said Ms. Rekers.

L19-IL2 is known to be safe in patients, with only mild side effects limited to injection site reactions. The new trial will look at the combination treatment in patients with oligometastatic solid tumors. “Our ultimate aim is to increase the time during which the disease does not progress by using this combination to bring about an immune response that will attack both the primary tumor and its metastases,” said Ms. Rekers.

Although reprogramming the immune system has only been feasible relatively recently, research to date seems to indicate that it is without damaging long-term effects. “We believe that the risk/benefit equation is likely to come down firmly on the side of benefit. We hope that this treatment will not only destroy tumors, but also enable the immune system to develop a memory that allows it to annihilate them in the future as well,” Ms Rekers concluded. 

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.


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