Cancer Immunotherapy Development
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|Personalized Therapies for Cancer||4 Main Steps of IO Application/Process||Promising Immunotherapies|
In the last decade, researchers have been studying the biological mechanisms that initiate and control cancer cell growth. This research includes an effort to understand the tumor microenvironment and the influence of checkpoint inhibitors, facilitating the development of therapies that are personalized for the treatment of the individual patient and their particular type of cancer.
Personalized Therapies for Cancer
|Type of Therapy||Description||Example of Drug|
|CAR-T||Activate a patient’s own T-cells to attack cancer cells||
|mAb||Antibodies developed in the lab that boost the immune system or attack a specific target on the cancer cell||
|Cytokines||Boost T-cell activity against cancer cells||
|Immune checkpoint inhibitors||Use checkpoint proteins to either activate or prevent an immune response||
|Oncolytic virus therapies||Genetically modified virus that, through injection into a cancerous lesion, replicates and causes cancer cells to rupture||
|Cancer vaccines||Vaccines that either restore the immune system’s ability to fight disease or prevent disease from developing||
Stages Of Immunotherapy Development
In this phase a target is identified and the mechanism behind the disease is examined. Researchers want to understand the tumor microenvironment and identify a specific target on tumor cells. To address the tumor target, the platform chosen could be an antibody, an ADC, immune cells, or modified immune cells.
In this stage of immuno-oncology research, potential therapeutics are designed and screened in cell and animal models for efficacy. The most promising therapeutics are further developed, which can include increasing efficacy and reducing potential immunogenicity and toxicity, to be ready for in human testing.
Clinical trials put the potential therapeutic through rigorous, regulated tests in humans. Safety of the selected therapy will be determined in early phases. In later phases, effectiveness of the therapeutic and side effects will be monitored and measured. At the same time, manufacturers begin to develop strategies to expand production of the therapeutic.
In the final stage, commercial processes are employed to manufacture the therapeutic, be it a biologic, a vaccine, or a cell therapy. Rigorous QC ensures the therapeutic is safe, effective and free from contaminants. Patient monitoring may be performed for some therapeutics to monitor side effects and measure the tumor’s response, allowing different treatment protocols to be implemented if needed.
CAR-T cell therapies (Chimeric Antigen Receptor) offer a new approach for the treatment of cancer. A patient’s immune cells are collected, genetically altered to recognize cancer antigens, multiplied, and returned to the patient. This type of therapy is a type of adoptive cell transfer and the alteration of the T-cells commonly occurs via retroviral transfer of the CAR gene into the T-cell. The engineered CAR-T cells’ cytokine-producing and cytolytic activity are now targeted against the tumor via specific antigens on the tumor cell surface. Only a few of these types of therapies have been approved for on-market use, however many more are in development.
Checkpoint Inhibitors as Targeted Therapy
Adaptive immune system T-cells play an important role in many immunotherapies. In healthy people T-cells are directed to identify and kill cancer cells. However cancer cells have developed a mechanism to hide from T-cells by expressing proteins on their surface to evade immune attack. Checkpoint inhibitors are monoclonal antibodies that reveal the cancer cells allow the T-cells to destroy the cancer cells. Programmed death protein (PD-1), its ligand PD-L1, and cytotoxic T-lymphocyte associated protein (CTLA-4) are the most characterized immune checkpoints, but are part of a much larger group of co-inhibitory molecules.
An interesting and innovative technology called BiTE (bi-speciic T-cell engager) is being developed at Amgen that engages the body’s endogenous T-cells to target malignant cells. Cancer cells have evolved multiple capabilities to evade detection by T-cells. BiTE technology overcomes this by physically linking the T-cells and cancer cells using an antibody that binds antigens expressed on the cancer cell and CD3 expressed on the T-cells. It’s clinical effectiveness is currently being investigated.
Cancer vaccines can either be preventative or therapeutic. Preventive vaccines are not classified as traditional immunotherapies. They are given prophylactically to protect a person from the viruses that may cause cancer, for example the HPV vaccine.Therapeutic vaccines strengthen the ability of a patient’s immune system to recognize and destroy cancer cell antigens. An example is the treatment called Provenge indicated for prostate cancer.
Another new process called Lm Technology, designed to activate the immune system using the body’s natural ability to recognize and attack bacterial infections, is being developed by Advaxis Immunotherapies. This technology alters a live, attenuated strain of Listeria monocytogenes to stimulate cancer-fighting T-cells to attack cancer antigens and reduce tumor defense mechanisms, in turn enabling the immune system to destroy cancer cells.