Pediatric cancer patients vaccinated against SARS-CoV-2-a clinical and laboratory follow-up.

BACKGROUND: Vaccination against SARS-CoV-2 is recommended for cancer patients. However, long-term data on the effectiveness in the pediatric setting are lacking. METHODS: Pediatric patients < 18 years on active treatment for cancer and without prior SARS-CoV-2 infection received three doses of an mRNA vaccine. The clinical course and humoral and cellular immunity were evaluated at the end of the follow-up period of ≥ 1 year after the third dose of vaccine. RESULTS: SARS-CoV-2 infection occurred in 17 of 19 analyzed patients (median age 16.5 years) during the follow-up period (median 17 months), but no severe symptoms were seen. At ≥ 1 year after the last SARS-CoV-2 antigen exposure, 4 of 17 patients had received the recommended booster vaccine. At the end of the follow-up period, all evaluable 15 patients had anti-SARS-CoV-2 receptor-binding domain IgG antibodies. Twelve of the 15 patients had neutralizing antibody titers ≥ 1:10 against the Delta variant and 12/15 and 13/15 against the BA.1 and BA.5 variants, respectively. Specific T cells against SARS-CoV-2 antigens were seen in 9/13 patients. CONCLUSIONS: Most SARS-CoV-2-vaccinated pediatric cancer patients had SARS-CoV-2 infections and limited interest in booster vaccination. At 1 year after the last antigen exposure, which was mostly an infection, humoral immune responses remained strong. TRIAL REGISTRATION: German Clinical Trials Register DRKS00025254, May 26, 2021.

Cellular dynamics following CAR T cell therapy are associated with response and toxicity in relapsed/refractory myeloma.

B-cell maturation antigen (BCMA)-targeting chimeric antigen receptor (CAR) T cells revolutionized the treatment of relapsed/refractory multiple myeloma (RRMM). However, data on cellular (CAR) T cell dynamics and the association with response, resistance or the occurrence of cytokine release syndrome (CRS) are limited. Therefore, we performed a comprehensive flow cytometry analysis of 27 RRMM patients treated with Idecabtagene vicleucel (Ide-cel) to assess the expansion capacity, persistence and effects on bystander cells of BCMA-targeting CAR T cells. Additionally, we addressed side effects, like cytokine release syndrome (CRS) and cytopenia. Our results show that in vivo expansion of CD8+ CAR T cells is correlated to response, however persistence is not essential for durable remission in RRMM patients. In addition, our data provide evidence, that an increased fraction of CD8+ T cells at day of leukapheresis in combination with successful lymphodepletion positively influence the outcome. We show that patients at risk for higher-grade CRS can be identified already prior to lymphodepletion. Our extensive characterization contributes to a better understanding of the dynamics and effects of BCMA-targeting CAR T cells, in order to predict the response of individual patients as well as side effects, which can be counteracted at an early stage or even prevented.

Detection of Immune Checkpoint Receptors - A Current Challenge in Clinical Flow Cytometry.

Immunological therapy principles are increasingly determining modern medicine. They are used to treat diseases of the immune system, for tumors, but also for infections, neurological diseases, and many others. Most of these therapies base on antibodies, but small molecules, soluble receptors or cells and modified cells are also used. The development of immune checkpoint inhibitors is amazingly fast. T-cell directed antibody therapies against PD-1 or CTLA-4 are already firmly established in the clinic. Further targets are constantly being added and it is becoming increasingly clear that their expression is not only relevant on T cells. Furthermore, we do not yet have any experience with the long-term systemic effects of the treatment. Flow cytometry can be used for diagnosis, monitoring, and detection of side effects. In this review, we focus on checkpoint molecules as target molecules and functional markers of cells of the innate and acquired immune system. However, for most of the interesting and potentially relevant parameters, there are still no test kits suitable for routine use. Here we give an overview of the detection of checkpoint molecules on immune cells in the peripheral blood and show examples of a possible design of antibody panels.