# Boosting T-cell immunity against COVID19  after CAR T-cell therapy by vaccination

> **NIH NIH P30** · UNIVERSITY OF COLORADO DENVER · 2020 · $155,500

## Abstract

Summary
 COVID19 is spreading rapidly across the globe and has caused more than 400,000 deaths, most of which
occurred in people with underlying comorbidities. Most patients presented for chimeric antigen receptor (CAR)
T-cell therapy against B-cell malignancy have poor immune function. Their immune function is further
suppressed by lymphodepleting regimens administered before CAR T-cell infusion and B-cell aplasia and
hypogammaglobulinemia caused by CAR T cells. Thus, patients treated with CAR T-cell therapy are at a higher
risk of COVID19-related morbidity and mortality. However, whether COVID19 vaccines induce immune
protection in patients treated with CAR T-cell therapy remains unknown. Studies have suggested that T-cell
immunity is critical to the control of infection by human coronaviruses. In addition, SARS-CoV-specific memory
T cells but not memory B cells persist in patients long after recovery from infection. Thus, given the importance
of antiviral T-cell immunity and depletion of B cells in patients treated with CAR T-cell therapy, it is critical to
understand how B-cell malignancy and CAR T-cell therapy affect long-term T-cell immunity induced by COVID19
vaccines. In the last twelve years, we have identified multiple signaling pathways essential for antiviral T-cell
immunity and gene signatures associated with effective long-term immune protection by antiviral T cells. In
particular, we have recently characterized a stem-like CD8 T cell population that resists T-cell exhaustion and
exhibits superior immunity against viruses and tumors. These stem-like CD8 T cells can be induced by
vaccination and persist decades in human after vaccination. Thus, stem-like CD8 T cells might endure the
immunosuppression caused by malignancy and cancer treatment and mediate potent immunity against SARS-
CoV-2. Here, we hypothesize that stem-like CD8 T cells induced by a COVID19 subunit vaccine mediate long-
term antiviral immunity after CAR T-cell therapy. Most current experimental models of CAR T-cell therapy rely
on severely immunocompromised mice lacking T and B cells and are not suitable for studying the immune
response induced by COVID19 vaccines. To evaluate the vaccine-induced T-cell immunity against SARS-CoV-
2 in CAR T-cell treated mice, we will employ a novel mouse model of anti-CD19 CAR T-cell therapy against B-
cell ALL using wildtype C57BL6 mice with intact immune system. Our study will shed light on the development
of vaccination strategy to generate effective immune protection against COVID19 for patients treated with CAR
T-cell therapy.

## Key facts

- **NIH application ID:** 10199682
- **Project number:** 3P30CA046934-32S7
- **Recipient organization:** UNIVERSITY OF COLORADO DENVER
- **Principal Investigator:** RICHARD D SCHULICK
- **Activity code:** P30 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $155,500
- **Award type:** 3
- **Project period:** 1997-04-04 → 2022-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10199682

## Citation

> US National Institutes of Health, RePORTER application 10199682, Boosting T-cell immunity against COVID19  after CAR T-cell therapy by vaccination (3P30CA046934-32S7). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10199682. Licensed CC0.

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