The CRIS Unit comprises three facilities, which have been set up to undertake the three most important phases in the development of new therapies, primarily:
- Translational Oncology Laboratory: studies are carried out in this laboratory to identify new targets and therapeutic strategies.
- New Compound Screening Laboratory: once new therapeutic strategies have been designed, the process of testing a large number of drugs or compounds is started. Using high-performance techniques, those with the greatest therapeutic value are identified and selected.
- Phase 1 Unit: phase 1 clinical trials will be carried out at this Unit in which the compounds developed at the previous facilities are evaluated in patients.
This highly efficient workflow makes this unit a point of reference in the development of new therapies.
Furthermore, it is highly beneficial to research projects that need the support of a certified molecular analysis facility. Therefore, it acts as a collaboration hub with other research laboratories in the development of joint projects (including many of the CRIS laboratories).
Furthermore, this Unit offers an ideal and appropriate facility for undertaking large clinical trials backed by pharmaceutical companies.
The Translational Oncology Laboratory:
In more detail, its objectives are as follows:
- Identify new therapeutic targets: in those tumours that require more specific or effective treatments, this laboratory will study the altered cellular mechanisms, which can be targeted with drugs.
- Evaluate the mechanisms of action of new compounds: the mechanisms of new compounds emerging in the scientific world will be developed and studied and their potential to treat different types of cancer will be established.
- Study mechanisms of resistance to existing compounds: tumour cells often end up adapting and resisting compounds and drugs that are beneficial at the start of treatment. Studying how this happens is the first step to avoiding it.
- Serve as a biomarker evaluation laboratory: biomarkers are characteristics of tumour cells, which enable a variety of factors to be identified: whether they belong to one type of tumour or another, whether they are more or less aggressive, whether or not they are susceptible to being attacked by certain drug, etc.
The New Compound Screening Laboratory:
Using high-throughput techniques, this laboratory has the capacity to evaluate large quantities of drugs and compounds on a huge scale. State-of-the-art techniques are used to detect those molecules (or combinations of therapies) with the greatest potential as new therapies.
It also enables the systematic study of new applications of compounds and drugs on different types of cancer, which have already been approved for other pathologies.
This enables considerable refinement of which compounds make it into clinical trials. By studying large amounts of similar compounds in the same experiments, only those with the best efficacy profile and minimal toxicity are selected.
Furthermore, this technology can be applied to projects involving virtually any type of cancer. For this reason, collaborations are being established with other CRIS research laboratories and even biotechnology companies that need to evaluate their new compounds and develop them before reaching the clinical stage.
Although the pandemic has dealt a sharp blow to research teams, the CRIS Unit for Experimental Therapies has been able to make significant progress.
One of the fields in which great advances have been made by the Unit regards immune cell therapies to fight ovarian tumours. The research teams are developing an extremely innovative strategy. The ultimate goal is for the tumour to be stopped from advancing using the patient’s own defences. This involves the following two factors:
- Firstly, it is important to understand that when a normal cell undergoes changes that result in it becoming a tumour, abnormal elements often appear on its surface. These abnormal elements are recognized by the immune system’s T lymphocytes, which destroy tumour cells. In this project tumour tissue is therefore extracted with the aim of identifying these abnormal molecules.
- Subsequently, T lymphocytes are extracted from the patient and exposed to these abnormal molecules. This means that the T lymphocytes become “trained” to destroy those cells with abnormal molecules.
In this way, we have cell therapies using the patients’ own cells, who are specialized in their own tumours. In other words, these are highly tailored treatments. This approach is being developed for several types of tumour, including breast and ovarian. To date, the Unit has successfully isolated lymphocytes from the tumours of 18 patients with ovarian cancer. It is currently sequencing and studying the tumours of these patients to find the abnormal molecules with which to target the lymphocytes.
In order to put this strategy into practice, the Unit is completing the necessary paperwork and working with the assessment bodies with the aim of providing this therapy to patients as soon as possible. This type of highly tailored approach, which could be available in as little as a year’s time, is absolutely novel. In fact, in Spain it is only being used in two other hospitals in compassionate use.
Furthermore, one of this Unit’s main strengths is developing its own Phase 1 clinical trials (click here to find out about the different phases of the cancer trials). It has recently begun enrolling patients in an innovative lung cancer immunotherapy trial. This trial consists of administering a molecule called Interleukin 2 (IL2) to patients, which the T lymphocytes normally use to multiply and become activate. What is interesting about this study is that a modified Interleukin 2 is used, which activates T lymphocytes but, unlike normal IL2, does not activate other cells responsible for stopping the lymphocytes. This modified IL2 gives us a tool to empower our own cells to fight lung cancer.
In addition to the aforementioned trial, the Unit is also preparing other cancer immunotherapy clinical trials. These trials will be directed at the molecular inhibitors of the T lymphocytes. The tumours usually activate these switches and turn off the lymphocytes. The treatments that prevent tumours from activating these switches are called Immune Checkpoint Inhibitors, and they have revolutionized cancer medicine.
In previous years, work has mainly been done with two of these inhibitors (PD1 and CTLA4), however recently additional inhibitors have been discovered, such as the so-called TIGIT, LAG3 etc. Trials are being prepared in the Unit to direct treatment at them, to prevent tumours from turning off the lymphocytes and to be able to effectively reject the tumours.