ALVR109: An allogeneic, off-the-shelf, SARS-CoV-2-specific T cell (VST) therapy candidate for COVID-19
COVID-19: A Global Public Health Issue and Role of T cells in Controlling SARS-CoV-2 Infections
SARS-CoV-2 infection causes the severe and life-threatening viral disease, COVID-19, creating a global public health issue. Studies to date estimate that the risk of mortality is up to 500% higher in patients 65 years of age or greater than in those aged 30 to 59 years. Other risk factors for severe COVID-19 include chronic lung or heart disease, hypertension, diabetes and underlying immune compromise.
Early evidence suggests that T cells play an important role in the body’s fight against COVID-19 and demonstrates that COVID-19 leads to depletion of endogenous T cells leading to acute immune deficiency, making infected individuals susceptible to developing, overwhelming and sometimes fatal pneumonia. Beyond the lungs, COVID-19 is a multi-organ disease that affects the heart, kidneys, brain, liver, and gastrointestinal tract, as well as causing blood clots. Over 80% of hospitalized patients with COVID-19 are lymphopenic, with reduced CD8+ and CD4+ T cell counts. These reductions in T cell counts correlate negatively with survival. Reduced T cell counts have been observed to be prevalent in older COVID-19 patients and those with severe illness, regardless of age. As further data on the immunogenicity of SARS-CoV-2 continues to emerge, the important protective role of SARS-CoV-2-specific T cells is increasingly being recognized.
Prevention of SARS-CoV-2 infection and clinical management of COVID-19 disease continue to evolve, and guidelines are updated regularly (e.g., https://www.covid19treatmentguidelines.nih.gov ; https://www.idsociety.org/practice-guideline/covid-19-guideline-treatment-and-management/). Vaccines are the most effective way to prevent infection, and monoclonal antibodies may be used for pre-exposure prophylaxis in individuals who may not be candidates for active immunization. Recommendations for COVID-19 treatment regimens are based on clinical severity and time from development of symptoms, and include immunomodulatory agents (e.g., corticosteroids, JAK inhibitors and IL-6 inhibitors), as well as antiviral agents (e.g., nirmatrelvir, remdesivir, molnupiravir) in addition to supportive care measures. Like other RNA viruses, SARS-CoV-2 is constantly evolving through random mutations, which can impact the efficacy of available preventive and therapeutic interventions. There is therefore still a need to develop alternative therapeutics that can maintain efficacy in the face of viral evolution. Novel therapeutics, including ALVR109, an allogeneic, off-the-shelf, SARS-CoV-2-specific T cell (VST) therapy candidate for COVID-19, may be of benefit to address this urgent unmet medical need. We are making ALVR109 available to physicians in response to compassionate use requests.
The development of ALVR109 demonstrates AlloVir’s ability to rapidly and efficiently develop new VST therapy candidates in response to emerging viral pathogens.