DNA vaccination: A challenging cancer therapeutic strategy
Immunotherapies have gained much attention nowadays in the treatment of cancer. Among them, therapeutic DNA cancer vaccines are now considered a very promising strategy to activate the immune system against cancer tumour.
DNA-mediated immunisation began in the 1990s. DNA vaccines have been developed to treat a variety of pathologies, including allergies, infectious diseases, and autoimmune diseases. To date, several preclinical and clinical studies have adopted strategies to better exploit the potential of DNA vaccination. The success in therapeutic vaccination is still limited even in preclinical models. It is due to the different mechanisms of resistance during tumour development tumour.
DNA vaccines alone are not able to overcome the tumour immune escape. Therefore, we prefer combination therapy (e.g., radiotherapy, endocrine therapy, chemotherapy, surgical removal) with this strategy.
The current challenges of cancer DNA vaccination strategy
Encoded antigen(s) selection: The antigen type, i.e., tumour-associated antigens (TAAs) or neoantigens. TAAs have been identified for most tumours, but immune tolerance can limit their efficiency. On the other hand, neoantigen identification is time consuming and expensive, and these antigens do not reflect the tumour heterogeneity in the individual patient (e.g., in metastasis).
Combination therapy and treatment schedule selection: Depending on the tumour type and patient-specific biomarkers, selection of an appropriate combination therapy and treatment schedule are challenging facts. We need to consider the time for the immune system to generate a specific immune response against the delivered antigen, the need for multiple doses of administration and the interaction with the combined therapy.
Availability of reliable preclinical model: Generally preclinical data serve the directions for the clinical settings. Humans and other experimental animals (e.g., mice, rats, rabbits, guinea pigs) have different immune system and tumour characteristics. Furthermore, housing, ethical regulation, and breeding difficulties limit the use of big animal models.
Personalisation of therapy: Immunotherapies have a variable response rates and side effects. In this case, identifying appropriate biomarkers is difficult because preclinical and clinical strategies are quite different. Recently, we have been using bioinformatics tools and new genomic and proteomic technologies have been used to predict specific tumour signatures, generating complex data sets that give rise to analytical challenges.
DNA vaccine therapy is unlikely to impact cancer outcomes as a single agent. Combinations with other strategies improve clinical outcomes compared to the single therapy. In the future, personalisation in the DNA vaccine design will be coupled with personalisation in the choice of the most appropriate combined therapy, following the analysis of single patient specificity and biomarkers that can predict the response to a specific agent.
Dr Muhammad Torequl Islam is an Assistant Professor of Pharmacy at the Bangabandhu Sheikh Mujibur Rahman Science and Technology University.
E-mail: dmt.islam@gmail.com