As part of World Cancer Day (4th Feb), the journal of Molecular Oncology invited researchers to take part in a writing competition aimed at highlighting how research in other areas of life sciences or technology influences the field of cancer biology and promotes cancer research. This entry, by Inês Simões Pinto, received the Second Honourable Mention.
Immunotherapy has emerged as a promising antitumor strategy since the immune system plays a critical role in detecting and eliminating cancer cells. With an increase in cancer incidence and prevalence, researchers have been exploring approaches that enhance the effectiveness of tumour regression but also minimize the harmful side effects associated with conventional treatments. Unlike chemotherapy and radiation, immunotherapy only targets cancerous cells, which is often better tolerated, and can be applicable to a wider range of cancers.
One recent immunological discovery is the chimeric antigen receptor (CAR) T-cell therapy which has already shown remarkable success in treating certain types of leukaemia and lymphoma. This approach involves engineering a patient's own immune cells to express the CAR that recognizes and attacks cancer cells, overcoming the immune escape mechanisms by tumours. However, the high costs of viral vectors to deliver the CAR gene limit access to this potentially life-saving therapy.
Nanotechnology could solve this problem by making cheaper and more accessible CAR gene carriers that can rapidly program T-cells to kill the target. Among them, cationic polymers show promise for various gene delivery platforms to T lymphocytes, as they have an easily modifiable surface and payload flexibility for hydrophilic and hydrophobic cargos.
Enter my project. The goal is to develop polymeric nanosystems capable of delivering the CAR gene efficiently and with reduced toxicity to T cells and unlock the full potential of this promising treatment for hepatocellular carcinoma cancer (HCC). To do this, we aim to generate mRNA encoding a CAR designed against HCC cells and packaged it in CD3-targeted polymer-based nanoparticles. Since covid-19, there has been growing interest in the potential of mRNA as a tool for cancer treatment due to its transient transgene expression that reduces the harmful effects of unlimited T-cell response caused by traditional gene therapy. On the other hand, nanosystems must be entered into T cells to achieve effective nucleic acid delivery. In this way, the nanoparticle is coupled with antibody anti-CD3, as CD3 is expressed by T cells and promotes receptor-mediated endocytosis by lymphocytes.
Our preliminary results in transfection efficiency in T cells are promising. Once we have successfully engineered T cells, the next step will be to evaluate the anticancer programming capabilities of CAR T cells to kill HCC cells in 2D and 3D models before testing it in animals. Moreover, by comparing the efficacy of our polymeric nanoparticles with conventional CAR T-cell therapy, we hope to demonstrate the potential of nanotechnology to enhance the effectiveness and safety of this cutting-edge treatment. With continued research and development, nanoparticles could become an essential tool for CAR T cell therapy for HCC cancer.
The combination of nanotechnology, immunology, cancer biology, and gene editing has the potential to revolutionize cancer treatment. As we continue to explore and develop new therapies, we must remember the power of interdisciplinary collaboration in unlocking new insights and breakthroughs. Together, we can create a world where cancer is no longer a death sentence.
Top image by Inês Simões Pinto
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