Reducing the SARS-CoV-2 viral load: Harnessing the power of T cells

May 04, 2020
T cells attack cancer cell
In cancer treatment, T cells are reprogrammed to kill cancer cells. Hollings Cancer Center researchers are applying this approach to COVID-19 in a clinical trial to test reprogramming T cells against the SARS-CoV-2 virus. iStock

Cancer researchers at the Medical University of South Carolina are joining the fight against COVID-19, the disease caused by the SARS-CoV-2 virus, but not by hunting for a vaccine or convalescent plasma therapy. Imagine a type of cell that can help your body kill the virus while your immune system recovers. This is the hope of a multidisciplinary team of MUSC researchers.

The team developing a clinical trial for this potential treatment is a strong collaboration between basic and clinical science researchers at Hollings Cancer Center led by Besim Ogretmen, Ph.D., the SmartState Endowed Chair in Lipidomics and Drug Discovery and director of the Developmental Cancer Therapeutics Program.

Ogretmen said their cancer backgrounds and innovative way of processing immune cells make them uniquely suited to this research. “Cancer is a cell that is foreign to the body, just like a virus is foreign. Our immune cells are wired to fight foreign things in our body, so we want to harness that power,” he said.

The national health emergency caused by the SARS-CoV-2 virus has been spurring innovation from all corners of research. While many research groups around the world are focusing on the generation of vaccines against SARS-CoV-2 and antibody-based COVID-19 treatments, this group is doing something different.

Early studies from China have shown that T cells—a type of immune cell with a key role in protecting a person from viruses and bacteria—play a part in COVID-19 recovery. Patients with the most severe disease have reduced T cell numbers, and patient recovery corresponds with T cell numbers returning to normal levels. However, T cell recovery depends on one important factor: viral load. Viral load is how many virus particles are in an infected person’s body. When the viral load is too high, the immune system becomes too weak to fight the disease.

Ogretmen and colleagues are using their expertise in T cells, based on their experience with cancer, to design a new treatment approach. Normally, they would use a patented technology approach to reprogram a cancer patient’s T cells to make them kill the cancer. Now, they plan to reprogram the T cells against the SARS-CoV-2 virus.

Dr. Besim Ogretmen 
Dr. Besim Ogretmen, leader of a multidisciplinary team testing a new COVID-19 treatment for critically sick patients, said this work is very important for cities and hospitals that have a lot of COVID-19 patients. Photo by Emma Vought

The reprogramming component of this cellular treatment is a critical step. In this context, reprogramming means improving the cells’ metabolic abilities so they do not get exhausted when they face the virus in a patient. The researchers will also use the SARS-CoV-2 “spike protein,” the part of the virus that protrudes from the viral particle surface, to identify the T cells that recognize the virus. These cells will then be injected into critically sick COVID-19 patients.

The MUSC-based clinical trial will be a two-step process. The first step is the collection and growth of the T cells that recognize the virus. This process is expected to begin within a month and will involve taking immune cells from approximately a dozen individuals who have recovered from COVID-19. Once the specific T cells are validated to ensure they work properly, they can be cryopreserved, or temporarily frozen.

The second step is a Phase I trial to assess safety. Three to four patients who are sick with COVID-19 will be injected with large numbers of the anti-viral T cells that were obtained from the previously recovered patients. The treatment will then move on to a Phase II trial to assess the effectiveness of this unique cellular treatment.

“We believe that this approach will give our clinician colleagues a treatment alternative,” Ogretmen said.

Although this therapy is based on repurposing a cancer treatment that uses a patient’s own cells, one important change is that this treatment will not do that. In the case of COVID-19, using a patient’s own T cells is not optimal since the reprogramming and growth protocol takes a month. Severely ill COVID-19 patients only have a 14-day treatment window before their body is too weak to continue functioning. Therefore, using T cells from recently recovered patients as donors is the solution.

The immune system of a COVID-19 patient is very weak. Therefore, it is unlikely that a COVID-19 patient’s body would negatively react to the anti-viral T cells from another person. The goal is for those special T cells to reduce the viral load by removing enough virus particles, which is not achieved well by convalescent plasma therapy, to allow the patient’s own immune system to recover.

A multidisciplinary group is essential in this type of endeavor, as expertise is needed from many basic science and clinical areas. This team includes researchers Ogretmen, Shikhar Mehrotra, Ph.D., and Xue-Zhong Yu, M.D., with expertise in cell biology and immunotherapy. It also includes physicians Michael Lilly, M.D., Brian Hess, M.D., Alice Boylan, M.D., and Cassandra Salgado, M.D., with expertise in cancer therapy, bone marrow transplantation, pulmonology and critical care medicine and infectious diseases.

One clinical hurdle is identifying which COVID-19 patients may be eligible to receive the 800 million to 1 billion anti-SARS-CoV-2 T cells that the researchers will infuse. Patients who are likely to recover by themselves should not be treated with this therapy; identifying the most at-risk patients is important.

Similarly, the team must choose the right T cell donors; they are currently focusing on collecting T cells from donors 35 years of age or younger to avoid T cells that have faced age-related stress. Previous cancer research has shown that T cells age very quickly, and aged T cells do not work as well as young T cells.

This study and the clinical trials could have far reaching impacts. “This work is very important for cities and hospitals that face heavy COVID-19 loads. This virus is going to be a part of our lives for a long time,” Ogretmen said.

But what about the vaccines that other research groups are developing? Vaccines work by training the immune system to recognize and attack a foreign substance, viral or bacterial, more quickly than it would without the vaccine. Therefore, individuals with poor immune systems do not benefit. Once a successful vaccine is widely available, this alternative cellular therapy approach to SARS-CoV-2 will still be needed. 

 

About the Author

Caroline Wallace

Keywords: Cancer, COVID-19, Research