Cancer Treatments

Programming the patient's own immune cells to recognize and destroy the cells constituting the cancerous tissue (immunotherapies and the CAR-T approach).

T-cells programmed to carry chimeric antigen receptors (CAR-T) represent a novel form of immunotherapy in which T-cells extracted from cancer patients are genetically modified to express a chimeric receptor that enables them to target cancer cells. CAR T-cells have emerged in recent years as one of the most exciting and innovative modalities for cancer treatment. CAR T-cell therapies are a crucial treatment option developed to eradicate advanced leukaemia and lymphomas, and to prevent cancer recurrence for many years. Research is ongoing to achieve similar success in solid tumours as well. In current CAR T-cell therapy, patients' autologous T-cells are utilized to generate a tumour antigen-specific CAR ex vivo, after which the CAR-T cells are reinfused into the patients. Recent studies have demonstrated that in-vivo CAR-T cells induced by nanocarriers loaded with CAR genes and gene-editing tools show highly promising effects for leukaemia regression (Smith, T., et al., 2017).

Şekil 1 – Fig. 1: CAR-T Cell Therapy

Labelling cancer cells with dual-specific monoclonal antibodies and facilitating their recognition by immune cells.

Monoclonal antibodies (mAbs) are Y-shaped proteins produced synthetically or by B lymphocytes, and they have the ability to bind to a specific molecular target. By designing humanized monoclonal antibodies (mAbs) against appropriate targets, anti-cancer effects have been achieved in preclinical models and patient studies. mAbs are one of the fastest-growing immunotherapy treatments. There are more than 22 FDA-approved mAb-based drugs for oncological diseases. Studies have shown that mAbs are biopharmaceuticals capable of improving the overall survival of cancer patients (Lu et al., 2020).

Development of mRNA vaccines against cancer.

Cancer vaccines are designed to elicit an immune response against tumour antigens. Cancer vaccines can be for preventive purposes, as is the case with HPV-induced cancers. Studies on developing vaccines as a cancer treatment are currently ongoing. Several mRNA vaccines are in various stages of clinical trials. The success of cancer vaccines depends on various factors, including the type of antigens used, the tumour microenvironment, the immune landscape of the tumour, and different vaccine formulations.

The development of patient-specific neoantigen cancer vaccines is generally carried out through the following steps:

1. Whole exome and RNA sequencing of tumour and normal cells is performed to identify somatic mutations (neoantigens) and their expression levels.
2. Patient-specific Human Leukocyte Antigen (HLA) alleles and the HLA binding affinity of potential neoantigens are determined.
3. The most promising candidate neoantigens are selected by filtering based on expression and HLA binding affinity, and the immunogenicity of the neoantigens is validated in vitro.
4. A vaccine containing the best neoantigens is created using a peptide complex, liposomal, or RNA delivery platform.

References:

• Smith, T., Stephan, S., Moffett, H. et al. In situ programming of leukaemia-specific T cells using synthetic DNA nanocarriers. Nature Nanotech 12, 813–820 (2017). https://doi.org/10.1038/nnano.2017.57
• Lu, RM., Hwang, YC., Liu, IJ. et al. Development of therapeutic antibodies for the treatment of diseases. J Biomed Sci 27, 1 (2020). https://doi.org/10.1186/s12929-019-0592-z