In the last two decades, viral vector-based therapies are gaining increasing attention as a promising strategy for cancer treatment. Studies in this field have explored the administration of viral vectors as agents for vaccines, gene therapy and more recently as oncolytic therapeutics. Here I have listed some of my work trying to understand how virotherapy works, what are the challenges in employing it as an anticancer therapy, and what can be done to make it a safe yet efficient treatment.
Systematic analysis on clinical studies assessing safety and efficacy of Onco-virotherapy
Through a systematic analysis we explored the clinical impact of onco-virotherapy compared to other cancer therapies by analyzing factors such as trial design, patient background, therapy design, delivery strategies, and study outcomes. We demonstrate that onco-virotherapy has proven to be clinically safe due to efforts in vector design, rational choices of therapeutic dosage and delivery strategies. However, the analysis reveals the need of more controlled trials in addition to including early-stage cancer patients and evaluation of immune responses.
Tumor‐derived extracellular vesicles boost melanoma response to oncolytic therapy (PT07.14.)
Tumor‐derived extracellular vesicles (TEVs) are active players in cancer establishment, progression and therapeutic resistance. For example, TEVs released by melanoma cells upon chemotherapy promote tumor outgrowth through nuclear reprogramming of both tumor and immune cells. Based on this, we hypothesized that the biological action of TEVs may predict treatment outcome. Our goal was thus to evaluate the possible pro‐ or anti‐tumoral effects of melanoma TEVs secreted during the oncolytic virotherapy based on Semliki Forest Virus (SFV) replicons.
Therapeutic resistance has been studied as a mechanism that allows the therapeutic-target to escape and evolve against the treatment, for example in the context of antibiotic resistance by pathogenic bacteria and resistance by tumors towards radiotherapy, chemotherapy, or immunotherapy.
Mechanisms of therapeutic resistance that impairs virotherapy
We assessed existing literature to compile the resistance mechanisms undermining efficacy of oncolytic virotherapy. We found that overall there is less focus on stuyding resistance to oncolytic virotherapy. Often cancer cell mediated interferon responses are explored as resistance mechanisms, however, there is a need to study resistance mechanisms related to stromal cells present in the tumor. Additionally, it is also necessary to investigate mechanisms regulating viral entry, spatio-temporal barriers, and cellular-epigenetic and -genetic responses in order to target such mechanisms for improvement of virotherapy efficacy.
Modeling the spatial dynamics of oncolytic virotherapy in the presence of virus-resistant tumor cells.
Oncolytic virotherapy is a promising form of cancer treatment that uses viruses to target, infect and kill cancer cells. Unfortunately, this form of therapy is often not effective, due to the occurrence of virus-resistant tumor cells. As it is challenging to assess the emergence and spread of resistance experimentally or in (pre)clinical studies, we designed a model that allows to study the spatial dynamics of virus-sensitive and virus-resistant tumor cells in various scenarios, and to predict the efficacy of virotherapy. By analysing the model systematically, we demonstrate the importance of 2D and 3D spatial interactions, the effects of viral properties (such as replication rate and range of infection), the properties of virus-resistant cancer cells (such as the cost of resistance), and the sensitivity of healthy (non-tumor) cells towards viral infection. Our goal is to provide a sound conceptual understanding of the mechanisms underlying therapeutic failure, which eventually may lead to the discovery of strategies that improve therapeutic efficacy. We therefore provide the reader with a graphical and a terminal interface of our model (executable on a local computer), allowing practitioners to reflect on their intuition regarding the complex yet fascinating dynamics of oncolytic virotherapy.
Gene Regulatory Networks
Immunoglobulins & Unfolded Protein Response
B cells orchestrate pro‐survival and pro‐apoptotic inputs to translate, fold, sort, secrete and recycle immunoglobulins, however B cells in some immunodeficient patients are predisposed to an overload of abnormally processed, misfolded immunoglobulins. We studied how dysregulation of unfolded protein response (UPR) in these B cells compared to the healthy control correlates with the disease phenotype. Read more.
My ‘bite-sized’ articles for general audience, approximately five minute reads, that share what is exciting in the field of Science.
- Read about evolutionary biology in bite-sized pieces @EvoBites
- Read about cancer biology in bite-sized pieces @OncoBites
- A chapter on Tumor Immunology (PDF in Portuguese) @CancerPlato
Synthetic Biology Projects and iGEM
Synthetic Biology is a field of Science focused on (re)designing biology using principles of engineering. The International Genetically Engineered Machine (iGEM) Foundation is an independent, non-profit organization dedicated to the advancement of synthetic biology, education and competition, and the development of an open community and collaboration. Find my contributions here.
For everyone curious in the microscopic world, have a look here.
Articles can also be accessed via: PUBMED, Scopus, ResearchGate, Google Scholar, ORCID, Web of Science