Cancer Vaccines: A Concoction Strategy to fight Leukemia

Chitra Roy, University of Calcutta

Leukemia is a malignancy of blood cells that starts to develop when the DNA of a single cell in the bone marrow mutates and fails to develop and function properly. These leukemia cells crowd out normal blood cells, making it difficult for the normal cells to do their job. Chronic and acute leukemia progress at a different pace so their treatment also differs accordingly. Treating leukemia is the most intensive of all cancer therapies because dealing with bone marrow would mean dealing with your body’s disease-fighting cells.

So, treatment strategies have to be designed in a way to achieve maximum benefit and minimum compromise to the immune system. Several strategies have been employed to treat leukemia. We know that T-cells are immune cells that help the body to fight against a foreign substance(antigen). In T-cell therapy, the T-cells from your blood are removed and specific receptors are added to those cells in a laboratory. These receptors will now allow the T-cells to recognize the cancer cells. These modified versions of T-cells are put back in the body of the patients where upon exposure to any cancer cells, these T-cells will recognize and destroy them! This therapy is called Chimeric Antigen Receptor (CAR) T-cell therapy. Although this is very promising, systematic exposure of CAR T-cells is also associated with various side effects like neurological toxicity, cytokine release syndrome, tumor lysis syndrome, all of which would again require additional treatments. 

Other strategies have also been employed where specific T-cells are activated in vivo where associated antigens are administered via local vaccination, but the antigens/epitope peptides which are used are poorly immunogenic, that is, they fail to trigger the appropriate amount of immune response required by T-cells to eliminate the antigen. So how can we overcome this? By using adjuvants! Adjuvants, as their name means ‘to help’ are a component present in many vaccines which helps to create a stronger immune response in an individual who received the vaccine. But again, their performance does not meet the expectations.

So, for a better and more reliable treatment option, can we look up to Cancer Vaccines for leukemia? The working principle of cancer vaccines differs from conventional vaccines to treat polio or measles.

Recently, a team of scientists from China, have come up with a major study in answering the above question, in the development of a new therapeutic vaccine against Leukemia. They used a PLA- poly (lactic acid) microsphere which is just like a nanoparticle-mediated drug delivery system. Since PLA is very biocompatible and biodegradable in our system, a good controlled release of any substance can be achieved. This research team exploited this drug delivery system, to deliver the antigen/epitope peptide in the body. To make their vaccine more clinically productive, they used mixed epitope peptide and PD-1 antibody, and co-encapsulated them into the PLA system, ultimately forming a microcapsule. We know that our immune system protects us from diseases and plays a significant role in clearing our body from any sort of unhealthy cell. So, it is very logical for our immune system to have a checkpoint to ensure that they don’t kill the healthy cells by mistake during such an immune response. But the clever cancer cells exactly exploit these checkpoints, so that they can easily evade from the immune cells. PD-1 (programmed cell death-1) is such a checkpoint protein that is present on the surface of the activated T-cells. The expression of PD-1 inhibits innate and adaptive responses, so if PD-1-antibody is used, it can bind to the PD-1 receptor of T-cell and modulate them. 

These scientists chose each component for the vaccine to make the maximum use of its property. So, the entire principle is: Once the vaccine is administered in the body, the Antigen Presenting Cells (APCs) are immediately recruited at the vaccination site. Since Poly (lactic acid)-PLA is a biodegradable polymer, with time it degrades in the body to release lactic acid and also releases the co-encapsulated compounds, epitope peptide, and PD-1 antibody. The APCs which were recruited initially take up the epitope peptide and the PD-1 goes and binds to the PD-1 receptor on the T-cell surface for modulation. These combinatory effects are a powerful concoction strategy that has shown significant improvement in activating specific Cytotoxic Lymphocytes. 

This microcapsule-based formulation showed excellent therapeutic effect having a great potential for future clinical translation.

Also read: COVID-19: Vaccine Development Probe

Suggested read: https://www.timesnownews.com/health/article/scientists-develop-new-precise-therapeutic-vaccine-for-leukaemia/667005

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