As City of Hope embarkes on the development of an experimental COVID-19 vaccine currently in a phase I clinical trial, ACCCBuzz spoke with Dr. Sanjeet Dadwal about the investigational vaccine’s safety and efficacy, potential emergency use authorization (EUA), and suitability for patients with cancer.
City of Hope is a comprehensive cancer center in Duarte, Calif., that has a long-standing history of vaccine study and development. Recently, City of Hope embarked on the development of an experimental COVID-19 vaccine currently in a phase I clinical trial. ACCCBuzz talked to Sanjeet Dadwal, MD—co-investigator of the trial, chief of the Division of Infectious Diseases at City of Hope, and co-chair of the medical center's Infection Control Committee—about the investigational vaccine's safety and efficacy, potential emergency use authorization (EUA), and suitability for patients with cancer.
Given that people who are immunocompromised have largely been excluded from the studies of authorized COVID-19 vaccines, such as those developed by Moderna and Pfizer-BioNTech, it is important that patients with cancer also have access to a safe and effective shield against SARS-CoV-2. Due to the design of the investigational City of Hope COVID-19 vaccine, patients who are immunocompromised may experience a better response. Currently, the vaccine is being studied in a phase I trial.
ACCCBuzz: Why is the City of Hope COVID-19 vaccine important?
Dr. Dadwal: City of Hope uses the Modified Vaccinia Ankara (MVA) [a vaccine delivery system for antigens], which has already been tested extensively in patients who have received hematopoietic cell transplants. MVA is also the vehicle we are using for our investigational COVID-19 vaccine. Studies have found that these [MVA-based] vaccines are very safe, effective, and are actually able to induce a good immune response even in patients with cancer who are otherwise immunocompromised. Using the same technology used to develop MVA-based vaccines, Dr. Diamond’s lab has developed a second-generation COVID-19 vaccine with two SARS-CoV-2 antigens. [Don J. Diamond, PhD— a professor in City of Hope’s Department of Hematology & Hematopoietic Cell Transplantation—is the principal investigator of City of Hope’s COVID-19 vaccine phase I clinical trial.]
This is a novel experimental vaccine because all of the other vaccines that have received emergency use authorization (EUA) use only the spike protein as the antigen for developing an immune response in the host. By using both the spike and the nucleocapsid proteins, we believe that the vaccine could be more immunogenic and could induce antibody responses and a T-cell response.
T-cells are the immune cells that form one’s immune memory and can be recalled by the body when you are exposed to the infection. So even when the antibody count decreases, these T-cells can still fight the virus. We believe the vaccine should work by inducing an immune response to two different targets and may have a lasting, more durable response in people.
ACCCBuzz: Tell us about the process of designing and studying the City of Hope COVID-19 vaccine.
Dr. Dadwal: As soon as COVID-19 hit, Dr. Diamond’s lab was on it. He began the animal studies for potential vaccines as the COVID pandemic spread. We had plans set for April or May 2020, and in June the optimal vaccine candidate was chosen. Animal studies showed a good antibody and cellular immune response. Manufacturing was completed by August, and applications were filed with the U.S. Food and Drug Administration by October 2020. The study officially started in November 2020.
The City of Hope investigational vaccine uses a technology that has been around for a long period of time and has been shown to be safe in many clinical trials. We also believe that the side effects should be less severe, and that the investigational vaccine could have a more robust and positive effect on the immune system, especially in immunocompromised patients.
The other thing is that animal studies are being done now in Dr. Diamond’s lab to look at the vaccine and the COVID-19 variants we have seen so far. We have targeted the two major COVID-19 components recognized by the immune system, namely the spike and the nucleocapside proteins, and we believe that it could be effective against known variants (because most of the mutations are in the spike protein). But it is too early to truly make this determination. Research data will prove the effectiveness of the vaccine on any COVID-19 variants.
ACCCBuzz: Can you comment on the process of designing and completing clinical trials, as well as next steps to apply for EUA?
Dr. Dadwal: We are in a phase I trial. As a co-investigator from a clinical standpoint, I help enroll patients into the study and follow up with them in the clinic. At the start, we began with a lower dose, followed by a medium dose, and then a high dose to study the immune response. The phase I study is designed to evaluate safety and to optimize the effective dosage. There were only a certain number of patients who were involved in the first dose finding. At the high-dose study, we began randomizing patients, so eight got the vaccine, and one received a placebo. Those first studies gave us the dosing mechanism: two doses per individual. Patients get the first dose at day zero and the second dose at day 28. We are currently trying to get 80 participants enrolled in the phase I trial.
ACCCBuzz: Is this vaccine a better option for immunocompromised patients, including patients with cancer?
Dr. Dadwal: We are still learning about the efficacy of COVID-19 vaccines in immunocompromised patients. But at this time, we know that the response can vary with different types of cancers, with those who have solid tumors (e.g., lung and colon cancers) doing better than those with blood cancer. In particular, patients with leukemia and lymphoma have a very poor response to vaccines. In part, this can be due to the response of the patient to treatment and time that has elapsed since their last treatment. At City of Hope, we will soon start a trial to determine the optimal immunization approach for our patients with blood cancer.
The current recommendation is to get vaccinated regardless of a patient’s immune status. In an ideal situation, you want to let patients with cancer or patients who have received transplants know what their chances of responding to the available vaccines is very likely or very low. If they get an EUA COVID-19 vaccine, they should not assume that they are going to be protected and can start going out in public without taking adequate safety measures.
