INTRODUCTION: The COVID-19 vaccine was designed to provide protection against infection by the severe respiratory coronavirus 2 (SARS-CoV-2) and coronavirus disease 2019 (COVID-19). However, the vaccine's efficacy can be compromised in patients with immunodeficiencies or the vaccine-induced immunoprotection suppressed by other comorbidity treatments, such as chemotherapy or immunotherapy. To enhance the protective role of the COVID-19 vaccine, we have investigated a combination of the COVID-19 vaccination with ex vivo enrichment and large-scale expansion of SARS-CoV-2 spike glycoprotein-reactive CD4+ and CD8+ T cells. METHODS: SARS-CoV-2-unexposed donors were vaccinated with two doses of the BNT162b2 SARS-CoV-2 vaccine. The peripheral blood mononuclear cells of the vaccinated donors were cell culture-enriched with T cells reactive to peptides derived from SARS-CoV-2 spike glycoprotein. The enriched cell cultures were large-scale expanded using the rapid expansion protocol (REP) and the peptide-reactive T cells were evaluated. RESULTS: We show that vaccination with the SARS-CoV-2 spike glycoprotein-based mRNA COVID-19 vaccine-induced humoral response against SARS-CoV-2 spike glycoprotein in all tested healthy SARS-CoV-2-unexposed donors. This humoral response was found to correlate with the ability of the donors' PBMCs to become enriched with SARS-CoV-2 spike glycoprotein-reactive CD4+ and CD8+ T cells. Using an 11-day REP, the enriched cell cultures were expanded nearly 1000-fold, and the proportions of the SARS-CoV-2 spike glycoprotein-reactive T cells increased. CONCLUSION: These findings show for the first time that the combination of the COVID-19 vaccination and ex vivo T cell large-scale expansion of SARS-CoV-2-reactive T cells could be a powerful tool for developing T cell-based adoptive cellular immunotherapy of COVID-19.

• Keywords
• COVID-19 vaccination, SARS-CoV-2, cellular immunity, ex vivo expansion, humoral immunity, spike glycoprotein-reactive,
• MeSH
• CD8-Positive T-Lymphocytes immunology   MeSH
• COVID-19 * immunology   MeSH
• Spike Glycoprotein, Coronavirus immunology   MeSH
• Glycoproteins MeSH
• Leukocytes, Mononuclear MeSH
• Humans MeSH
• Antibodies, Viral MeSH
• SARS-CoV-2 MeSH
• BNT162 Vaccine MeSH
• COVID-19 Vaccines * MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Names of Substances
• Spike Glycoprotein, Coronavirus MeSH
• Glycoproteins MeSH
• Antibodies, Viral MeSH
• spike protein, SARS-CoV-2 MeSH Browser
• BNT162 Vaccine MeSH
• COVID-19 Vaccines * MeSH

The adaptive immune response to severe acute respiratory coronavirus 2 (SARS-CoV-2) is important for vaccine development and in the recovery from coronavirus disease 2019 (COVID-19). Men and cancer patients have been reported to be at higher risks of contracting the virus and developing the more severe forms of COVID-19. Prostate cancer (PCa) may be associated with both of these risks. We show that CD4+ T cells of SARS-CoV-2-unexposed patients with hormone-refractory (HR) metastatic PCa had decreased CD4+ T cell immune responses to antigens from SARS-CoV-2 spike glycoprotein but not from the spiked glycoprotein of the 'common cold'-associated human coronavirus 229E (HCoV-229E) as compared with healthy male volunteers who responded comparably to both HCoV-229E- and SARS-CoV-2-derived antigens. Moreover, the HCoV-229E spike glycoprotein antigen-elicited CD4+ T cell immune responses cross-reacted with the SARS-CoV-2 spiked glycoprotein antigens. PCa patients may have impaired responses to the vaccination, and the cross-reactivity can mediate antibody-dependent enhancement (ADE) of COVID-19. These findings highlight the potential for increased vulnerability of PCa patients to COVID-19.

• Keywords
• COVID-19, HCoV-229E, SARS-CoV-2, prostate cancer, spike glycoprotein,
• MeSH
• Adaptive Immunity MeSH
• CD4-Positive T-Lymphocytes immunology   MeSH
• CD8-Positive T-Lymphocytes immunology   MeSH
• COVID-19 immunology   virology   MeSH
• Cytokines immunology   MeSH
• Spike Glycoprotein, Coronavirus immunology   MeSH
• Middle Aged MeSH
• Humans MeSH
• Coronavirus 229E, Human immunology   MeSH
• Prostatic Neoplasms immunology   pathology   MeSH
• SARS-CoV-2 immunology   MeSH
• Aged MeSH
• Cross Reactions MeSH
• Check Tag
• Middle Aged MeSH
• Humans MeSH
• Male MeSH
• Aged MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Names of Substances
• Cytokines MeSH
• Spike Glycoprotein, Coronavirus MeSH
• spike protein, SARS-CoV-2 MeSH Browser

Upregulated Wnt/β-catenin signaling is associated with increased cancer cell resistance and cancer cell-elicited immunosuppression. In non-neoplastic immune cells, upregulated Wnt/β-catenin is, however, associated with either immunosuppression or immunostimulation. Therefore, it is difficult to predict the therapeutic impact inhibitors of Wnt/β-catenin signaling will have when combined with cancer immunotherapy. Here, we evaluated the benefit(s) of the Wnt/β-catenin signaling inhibitor XAV939 in the in vitro elimination of LNCaP prostate cancer cells when cocultured with lymphocytes from patients with localized biochemically recurrent prostate cancer (BRPCa). We found that 5 µM XAV939 inhibited β-catenin translocation to the nucleus in LNCaP cells and CD4+ BRPCa lymphocytes without affecting their proliferation and viability. Preconditioning BRPCa lymphocytes with 5 µM XAV939 accelerated the elimination of LNCaP cells during the coculturing. However, during subsequent re-coculturing with fresh LNCaP cells, BRPCa lymphocytes were no longer able to eliminate LNCaP cells unless coculturing and re-coculturing were performed in the presence of 5 µM XAV939. Comparable results were obtained for PC-3 prostate cancer cells. These findings provide a rationale for combining cell-based immunotherapy of PCa with inhibitors of Wnt/β-catenin signaling.

• MeSH
• beta Catenin antagonists & inhibitors   metabolism   MeSH
• PC-3 Cells MeSH
• CD4-Positive T-Lymphocytes drug effects   immunology   MeSH
• Heterocyclic Compounds, 3-Ring pharmacology   MeSH
• Immunotherapy methods   MeSH
• Middle Aged MeSH
• Humans MeSH
• Cell Line, Tumor MeSH
• Prostatic Neoplasms drug therapy   genetics   pathology   MeSH
• Wnt Proteins antagonists & inhibitors   metabolism   MeSH
• Antineoplastic Agents pharmacology   MeSH
• Aged MeSH
• Wnt Signaling Pathway drug effects   MeSH
• T-Lymphocytes cytology   immunology   MeSH
• Tankyrases antagonists & inhibitors   MeSH
• Check Tag
• Middle Aged MeSH
• Humans MeSH
• Male MeSH
• Aged MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Names of Substances
• beta Catenin MeSH
• CTNNB1 protein, human MeSH Browser
• Heterocyclic Compounds, 3-Ring MeSH
• Wnt Proteins MeSH
• Antineoplastic Agents MeSH
• Tankyrases MeSH
• XAV939 MeSH Browser