In today’s article, we’re pleased to inform you about two excellent Italian biomedical research initiatives that are joining forces in applied cellular immunotherapy, in order to offer new hope to cancer patients.
We talk about this with Dr. Roberta Sommaggio, a graduate in Medical Biotechnology and a PhD in Biomedicine (with a specialty in Immunology), who currently works at the Istituto Oncologico Veneto (IOV) in Padua; also with Dr. Giuseppe Astori, Head of the Advanced Cell Therapy Laboratory at the Complex Hematology Unit of the Hospital of Vicenza.
Dr. Astori has previously made a valuable contribution to S4L in a recent article, describing the use of mesenchymal cells as therapy for COVID-19-related pneumonia.
This time he spoke with us, together with Dr. Sommaggio, about a project that is a strong collaboration between two public laboratories, and that has combined their very different capabilities.
Dr. Sommaggio and Dr. Astori: What is the basis of this collaboration?
Dr. Sommaggio: “The project focuses on the expansion of cytokine-induced killer cells, called CIK (Cytokine-Induced Killer cells) generated in large quantities from the patient’s blood — appropriately stimulated with cytokines. After 14 days of cell culture, the CIKs become “cytotoxic” (i.e. able to destroy tumor cells).
CIKs have already been used in the clinic, but what we wanted to achieve is to increase their effectiveness. We knew that these cells express on the cell membrane the CD16 receptor, which is a protein capable of recognizing certain molecules called monoclonal antibodies.
These antibodies, in turn, recognize with absolute precision certain tumor cells in a key-type mechanism. In practice, monoclonal antibodies act as a kind of bridge between CIK cells and target cancer cells, allowing CIK cells to detect and kill cancer cells with high efficiency. The target of the therapy we’re currently focusing on is a blood cancer called Diffuse Large B Cell Lymphoma (DLBCL)”.
Dr. Astori: “It’s the same tumor that is treated with CAR-T cells; an acronym for “Chimeric Antigen Receptor T cells” which represent the last frontier of immunotherapy. However, CAR-T can only be administered to patients who are able to withstand the severe side effects. It’s clear that our researchers don’t want to replace the CAR-T therapy, but to complement it, in cases where the patient doesn’t meet the criteria needed to receive it. This would cover some of those patients who would otherwise be left without a valid therapeutic alternative”.
Dr. Sommaggio: “Another very important feature of CIK cell therapy is its potential versatility: in fact, one could think of using a monoclonal antibody specific to the type of tumor of interest each time. This is a bit like if the monoclonal antibody acts as a GPS, in order to target the killer cell, the CIK, to the target”.
Can any tumor be treated with CIK cells?
Dr. Sommaggio: “Potentially, this treatment could be effective on any tumor if we had the right key (i.e. the monoclonal antibody directed at that specific tumor). For example, we performed a pre-clinical study on mice with highly aggressive breast tumors called “triple negative” and highly metastasizing. The work was recently published in OncoImmunology (DOI: 10.1080/2162402X.2020.1777046). Using a commercially available antibody, we were able to demonstrate that CIK can be effective, even on a tumor like this is otherwise difficult to treat”.
What is the strength of this study?
Dr. Astori: “In addition to the scientific validity and inherent therapeutic value, this study demonstrates the importance of collaboration between two different (but closely related) realities, such as the IOV and the Advanced Cellular Therapy Laboratory. The first one represents excellence in research, and the second is among the few Italian laboratories authorized by the Italian Medicine Agency to produce cell-based medicines, the so-called ‘Advanced Therapy Medicinal Products’.
Without these synergies, research would have remained one of the many scientific works published and perhaps an end in itself. Instead, thanks to the spirit of collaboration fostered by the Deputy Scientific Director of the IOV, Dr. Antonio Rosato and the Director of Hematology Vicenza, Dr. Marco Ruggeri, it was possible to build a path of translation from research to the production of the drug-cell. The next step will be the clinical trial, which we expect to start sometime in 2021. This will be possible, thanks to the continuous interaction that exists between researchers and hematologists at the Hospital of Vicenza, the IOV and the Azienda Ospedaliera Universitaria di Verona“.
What are some advantages of CIK therapy for patients?
Dr. Sommaggio: “There are many and are equally important. For example:
- The cells come from the patients themselves (autologous) and are generated by a simple blood sample
- They are not rejected by the body
- They do not have to be engineered using lentiviral vectors as is the case with CAR-T with all the associated technical difficulties
- Their production has a very low cost when compared to CAR-T
- It is possible to produce large quantities in a short time
They’re not covered by patent; the protocol is published and therefore available to the scientific community”.
What is the most motivating aspect of your work?
Dr. Sommaggio: “Certainly the possibility of transferring basic research into something that can be useful for the patient. If even one person could be saved from treatment with CIK, it would be a great motivation to develop additional studies”.
We’d like to conclude this interview, saying that today more than ever, it’s necessary to develop synergies between research, drug-cell production and clinics, in order to accelerate the transfer of basic research to the patient and therefore optimize the always scarce financial resources available. In an increasingly competitive world, and where trials are very expensive, a laboratory alone can make very little progress, and never before has a union like this one provided such strength!
It is thanks to people like Dr. Sommaggio, Dr. Astori and all their collaborators who dedicate themselves with great commitment and professionalism to their work; that the great ideas born in the laboratory can turn into useful therapies for all of us. The least we can do is thank them!
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