Data are scarce regarding both safety and immunogenicity of the BNT162b2 mRNA COVID-19 vaccine in patients undergoing immune cell therapy, thus we prospectively evaluated these 2 domains in patients receiving this vaccine after allogeneic HCT (n=66) or after CD19-based CART therapy (n=14). Overall, vaccine was well tolerated, with mild non-hematologic vaccine-reported adverse events in minority of the patients. 12% (after first dose) and 10% (after second dose) of the patients developed cytopenia and there were 3 cases GVHD exacerbation after each dose. A single case of impending graft rejection was summarized as possibly related. Evaluation of immunogenicity showed that 57% of patients after CART infusion and 75% patients after allogeneic HCT had evidence of humoral and/or cellular response to the vaccine. On cox regression model, longer time from infusion of cells, female sex, and higher CD19 + cells were associated with a positive humoral response, whereas higher CD4 + /CD8 + ratiowas correlated with a positive cellular response, confirmed by ELISpot test. We conclude that BNT162b2 mRNA COVID-19 vaccine has impressive immunogenicity in patients after allogeneic HCT or CART. Adverse events were mostly mild and transient, but some significant hematologic events were observed, hence, patients should be closely monitored.

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Selectin ligands are crucial components in the interaction between endothelial cells and extravasating cancer cells and, thus, play an important role in metastasis formation. Headand-neck squamous cell carcinoma (HNSCC) variants expressing high levels of E48, a human Ly-6 protein (E48 hi ), expressed higher levels of the fucose-generating FX enzyme and of the fucosylated E-selectin ligand sLe a than cells expressing low levels of E48 (E48 lo ). Signaling through E48 upregulated expression levels of these molecules in HNSCC. Head-and-neck squamous cell carcinoma (HNSCC) is a major health problem. About 500,000 new cases are diagnosed annually worldwide. 1,2 Despite advances made in the diagnosis and treatment of HNSCC during the last decades, the treatment efficay and associated morbidity as well as the 5-year survival rate have only marginally improved. 3,4 However, the type of relapse is gradually shifting from locoregional recurrence to distant metastasis. 1 It is therefore critically important to develop novel treatment modalities. Advancement in the development of new forms of therapy depends to a large extent on the availability of additional information on and a profound understanding of the molecular and cellular mechanisms involved in HNSCC carcinogenesis and progression. There is already ample information on the genetic alterations in HNSCC, including mutation of p53, 5 amplification of PRAD-1 (chromosome 11q13) 6 and frequent LOH on 9p, 3p, 17p, 8p, 13q and 18q. 7 These alterations characterize specific histopathologic stages of HNSCC. However, the molecular mechanisms involved in lymphogenic and hematogenic metastasis formation remain unknown. These parameters obviously determine the prognosis of the disease.MAb E48 was 1 of several developed to detect and treat minimal residual HNSCC following primary treatment. 8 It recognizes an outer membrane antigen, expressed by HNSCC. This antigen was characterized by cDNA cloning 9 and proved to be a GPIanchored membrane protein expressed by squamous cells. E48 is highly (nearly 70%) homologous to the murine ThB protein, a member of the Ly-6 gene family. 9 -11 E48 maps on human chromosome 8q24, 9 the syntenic locus of mouse chromosome 15E, to which the mouse Ly-6 gene family has been mapped. 11 Whereas both E48 and ThB are expressed on keratinocytes of squamous epithelia, 9 they differ in lymphocyte expression. ThB is expressed by mouse lymphocytes, whereas E48 is not expressed by human lymphocytes. 12 The function of E48 on keratinocytes of squamous epithelia remains unclear, though it might be involved in cellular adhesion. 9 Shortly after the cloning of cDNA encoding the E48 antigen, several additional human Ly-6 genes were cloned. [13][14][15][16][17] Our laboratory reported previously on a linkage between the overexpression of certain Ly-6 proteins on mouse tumor cells and a high-malignancy phenotype of such cells. 18 -20 In view of the association of Ly-6 with a high-malignancy phenotype of mouse tumors, it was of interest to study the role, if any, pla...

Murine Ly-6 is a molecule expressed by various cells, including several types of hematopoietic cells such as pluripotent stem cells, and activated T cells. Ly-6 is also expressed on tumor cells originating from a variety of tissues. Preliminary observations suggested that the expression of Ly-6A/E is up-regulated on highly tumorigenic variants of polyoma-virus(PyV)-transformed BALB/c 3T3 cells as compared with weakly tumorigenic variants. On the basis of these observations, we sorted PyV-transformed A3C cells or DA3 mammary adenocarcinoma cells into stable sub-populations expressing high or low levels of membrane or mRNA Ly-6A/E. In vivo studies indicated that the high-Ly-6A/E-expressing cells in both tumor systems expressed a considerably more malignant phenotype (higher efficiency in local tumor production as well as in lung colonization) than low-Ly-6A/E expressors. Since the high-Ly-6A/E expressors did not exhibit any growth advantage in vitro over low Ly-6A/E expressors, we concluded that interactions of the former cells with micro-environmental factors operating in vivo (e.g., Ly-6A/E ligands) conferred upon these cells a highly malignant phenotype. Apart from the difference in Ly-6A/E expression, no other phenotypic characteristics distinguished highly from weakly malignant tumor cells. Similarly to T cells, where antibodies to Ly-6 transduce (or co-transduce) a proliferative signal, antibodies to Ly-6A/E were found to transduce a mitogenic signal to high-Ly-6A/E-expressing tumor cells but not to low-Ly-6A/E expressors. Taken together, these results show that Ly-6A/E expression is directly or indirectly associated in vivo with a highly malignant phenotype of 2 types of non-lymphoid murine tumors.