Background Activity and safety of the SARS-CoV2 BNT162b2 vaccine in actively treated patients with solid tumors is currently unknown. Methods We conducted a retrospective study of 326 patients with solid tumors treated with anti-cancer medications to determine the proportion of cancer patients with immunogenicity against SARS-CoV2, following two doses of the BNT162b2 vaccine. Control group was comprised of 164 vaccinated healthy adults. Anti-SARS-CoV-2 S IgG (Immunoglobulin G) antibodies (Abs) were measured, using level>50 AU/ml as cutoff for seropositivity. Adverse effects were collected using a questionnaire. All statistical tests were 2-sided. Results Most patients (205, 62.9%) were treated with chemotherapy, either alone or with additional therapy, 55 (16.9%) were treated with immune checkpoint inhibitors (ICI) and 38 (11.7%) with targeted therapy alone, 28 (8.6%) received other combinations. The vaccine was well tolerated and no severe side effects were reported. Among patients with cancer 39 (11.9%) were seronegative, compared to 5 (3.0%) of the control group (P=0.001). Median IgG titers were statistically significant lower among patients with cancer compared to control (931 AU/ml vs. 2817 AU/ml, P=0.003). Seronegativity proportions were higher in the chemotherapy treated group (19, 18.8%) compared to the ICI-treated patients (5, 9.1%) and to those treated with targeted therapy (1, 2.6%) (P=0.02. Titers were also statistically significant different among treatment types (P=0.002). Conclusion The BNT162b2 vaccine is safe and effective in actively treated patients with cancer. The relatively lower antibody titers and lower proportion of seropositive patients, especially among chemotherapy treated patients, call for continuing the use of personal protective measures in these patients, even following vaccination.

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Klotho is an anti-aging transmembrane protein, which can be shed and function as a hormone. Accumulating data indicate klotho as a tumor suppressor in a wide array of malignancies and indicate the subdomain KL1 as the active region of the protein. We aimed to study the role of klotho as a tumor suppressor in colorectal cancer. Bioinformatics analyses of TCGA datasets indicated reduced klotho mRNA levels in human colorectal cancer, along with negative regulation of klotho expression by hypermethylation of the promoter and 1st exon, and hypomethylation of an area within the gene. Overexpression or treatment with klotho or KL1 inhibited proliferation of colorectal cancer cells in vitro. The in vivo activity of klotho and KL1 was examined using two models recapitulating development of tumors in the normal colonic environment of immune-competent mice. Treatment with klotho inhibited formation of colon polyps induced by the carcinogen azoxymethane, and KL1 treatment slowed growth of orthotopically-implanted colorectal tumors. Gene expression array revealed that klotho and KL1 expression enhanced the unfolded protein response (UPR) and this was further established by increased levels of spliced XBP1, GRP78 and phosphorylated-eIF2α. Furthermore, attenuation of the UPR partially abrogated klotho tumor suppressor activity. In conclusion, this study indicates klotho as a tumor suppressor in colorectal cancer and identifies, for the first time, the UPR as a pathway mediating klotho activities in cancer. These data suggest that administration of exogenous klotho or KL1 may serve as a novel strategy for prevention and treatment of colorectal cancer.