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CAR-T Cell Immunotherapy

Introduction

We, as humans, have conquered many cancers including prostate, thyroid, testicular, melanoma, and breast , and are still struggling to find new therapies to enhance the quality of life of the patients. Radiation therapy, chemotherapy, and surgery were the painful, main treatments before we discovered immunotherapy. Immunotherapy uses the immune system to kill cancer, minimizing the painful period that patients undergo.


What is a CAR-T Cell?

CAR-T cells incorporate chimeric antigen receptors. As explained by the National Cancer Institute, chimeric means having parts of different origins like combining antibodies and activated parts of a T cell into a single unit. The prefix of antigen is anti- (against) and the suffix is -gen (the thing that produces), indicating the function of antigen is that it orders the immune system to produce antibodies. Receptors receive orders from external stimuli and deliver a signal to a sensory nerve.


Why is it the Most Effective Immunotherapy?

There are other immunotherapy methods such as Dendritic cell and NK cell immunotherapy, but CAR-T Cell immunotherapy is the most effective cure among them because of clonal expansion, accurate targeting, and memory system.


First, thanks to clonal expansion, it creates T-cells exponentially. As stated in Anatomy & Physiology by Boundless, clonal expansion indicates the proliferation of B-cell and T-cell activated by clonal selection to produce a clone of identical cells. In other words, T-cells combine with certain antibodies and activate to form intensive armies of anticancer cures. Second, CAR-T cell immunotherapy targets the tumor markers accurately. They are substances that react to cancer cells or noncancer cells and give cancer information. CAR detects tumor markers like a sniper skilled at aiming at the target. Also, the top of CAR is designed to look similar to antigens of cancers. Lastly, the memory system helps to remember the antigen of the cancer it met. This is expected to fight continuously and to stop T-cells from being tired of fighting against the cancer.





Process of CAR-T Cell Immunotherapy

Step 1. Collect blood

Step 2. Extract T-cell and return the remaining blood to the patient

Step 3. Transfer genes to make the T-cell have chimeric antigen receptors by using an adenovirus vector

Step 4. Proliferate the CAR-T cells

Step 5. Inject the proliferated CAR-T cells into the patient


Limits of CAR-T Cell Therapy

Even though this therapy has a big advantage of minimizing the pain in curing cancer, in the ELIANA study, 7.6% of patients could not receive a cell due to product-related issues. T-cells could be produced in abnormal states or low states. Generally, it takes about 15~25 days to make CAR-T cells, however, it aggravates the conditions of patients. Also, CAR-T cell therapy can only cure particular types of blood cancer, leaving other cancers to be uncured. Furthermore, the cost is not affordable to most people. The first FDA-approved PD CAR-T cell product from Novartis is priced at $475,000 US per patient.


The Synergy between CAR-T Cell Immunotherapy and CRISPR

To push the envelope, researchers found allogeneic CAR T-cell therapy that uses healthy people’s T-cells with CRISPR, a tool to edit genes. This gave patients that faced the limitation of CAR-T cell therapy hope. Off-the-shelf CAR-T cells are now available to make standardized drugs and lower the price. Moreover, this technology has made it possible to treat solid cancer that has many antigens.


Side Effects

  • Graft versus host disease

  • Brittle nails

  • Rippled skin

  • Speech problems

  • Tremors

  • Delirium

  • Seizures

* According to the National Cancer Institute, some side effects can be severe or fatal.


Conclusion

Norman Cousins said, “The more serious the illness, the more important it is for you to fight back, mobilizing all your resources-spiritual, emotional, intellectual, physical.” If someone around you is having a hard time with cancer, encourage them and fight back together.



Reference

Graham C, Jozwik A, Pepper A, Benjamin R. Allogeneic CAR-T Cells: More than Ease of Access? Cells. 2018 Oct 1;7(10):155. doi: 10.3390/cells7100155. PMID: 30275435; PMCID: PMC6210057.


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