Simple SummaryChildren with cancer experience a more severe SARS-CoV-2 infection and more often die due to COVID-19 than their healthy peers. Vaccination against SARS-CoV-2 is therefore recommend in children with cancer but little is known about their immune response following vaccination. With this study we aimed to investigate the effect of a 2- and/or 3-dose vaccination series in children who are undergoing active cancer treatment and in children that finished their cancer treatment. The results from this study show that compared to 2-dose vaccination, a 3-dose vaccination series was more effective in boosting antibody levels and is therefore of value for children undergoing active cancer treatment. The findings from this study provide evidence for the significance of COVID-19 vaccination in children undergoing cancer treatment and are also important for future vaccination strategies in children with cancer.AbstractCOVID-19 vaccinations are recommended for children with cancer but data on their vaccination response is scarce. This study assesses the antibody and T-cell response following a 2- or 3-dose vaccination with BNT162b2 mRNA COVID-19 vaccine in children (5–17 years) with cancer. For the antibody response, participants with a serum concentration of anti-SARS-CoV-2 spike 1 antibodies of >300 binding antibody units per milliliter were classified as good responders. For the T-cell response, categorization was based on spike S1 specific interferon-gamma release with good responders having >200 milli-international units per milliliter. The patients were categorized as being treated with chemo/immunotherapy for less than 6 weeks (Tx < 6 weeks) or more than 6 weeks (Tx > 6 weeks) before the first immunization event. In 46 patients given a 2-dose vaccination series, the percentage of good antibody and good T-cell responders was 39.3% and 73.7% in patients with Tx < 6 weeks and 94.4% and 100% in patients with Tx > 6 weeks, respectively. An additional 3rd vaccination in 16 patients with Tx < 6 weeks, increased the percentage of good antibody responders to 70% with no change in T-cell response. A 3-dose vaccination series effectively boosted antibody levels and is of value for patients undergoing active cancer treatment.