COVID-19 peptide specific T-cells and methods of treating and preventing COVID-19
The invention relates to pharmaceutical compositions that contain COVID-19 peptide specific cytotoxic T cells, and to methods for treating or preventing COVID-19 infection.
1. A method of treating COVID-19 infection, comprising administering to a human patient in need thereof an effective amount of cells comprising COVID-19 peptide specific cytotoxic T lymphocytes (CTLs) that are specifically enriched cells reactive to COVID-19 peptides, wherein said CTLs are sensitized against multiple peptides restricted against a single HLA allele by in vitro stimulation, wherein at least 20% of said CTLs are reactive to COVID-19 peptides, and wherein said cells comprise less than 2.5% of naïve T cells, monocytes, NK cells, or any combination thereof.
2. The method of claim 1 , wherein said patient is an elderly or immunocompromised patient.
3. The method of claim 1 , wherein said administering is done by intravenous infusion.
4. The method of claim 3 , wherein said infusion is delivered to the patient through a central line or midline.
5. The method of claim 1 , wherein said COVID-19 peptide specific CTLs are from a single donor.
6. The method of claim 1 , wherein said COVID-19 peptide specific CTLs were sensitized against one or more peptides restricted against an HLA-A1 allele.
7. The method of claim 6 , wherein said one or more peptides are selected from the list consisting of SEQ ID NO:1, SEQ ID NO:2, SEQ ID NO:3, SEQ ID NO:4, SEQ ID NO:5, SEQ ID NO:6, SEQ ID NO:7, SEQ ID NO:8, SEQ ID NO:9, SEQ ID NO:10, SEQ ID NO:11, SEQ ID NO:12, SEQ ID NO:13, SEQ ID NO:14, SEQ ID NO:15, SEQ ID NO:16, SEQ ID NO:17, SEQ ID NO:18, SEQ ID NO:19, SEQ ID NO:20, SEQ ID NO:21, SEQ ID NO:22, SEQ ID NO:23, SEQ ID NO:24, SEQ ID NO:25, SEQ ID NO:26, SEQ ID NO:27, or a combination thereof.
8. The method of claim 1 , wherein said COVID-19 peptide specific CTLs were sensitized against one or more peptides restricted against an HLA-A2 allele.
9. The method of claim 8 , wherein said one or more peptides are selected from the list consisting of SEQ ID NO:28, SEQ ID NO:29, SEQ ID NO:30, SEQ ID NO:31, SEQ ID NO:32, SEQ ID NO:33, SEQ ID NO:34, SEQ ID NO:35, SEQ ID NO:36, SEQ ID NO:37, SEQ ID NO:38, SEQ ID NO:39, SEQ ID NO:40, SEQ ID NO:41, SEQ ID NO:42, SEQ ID NO:43, SEQ ID NO:44, or a combination thereof.
10. The method of claim 1 , wherein said COVID-19 peptide specific CTLs were sensitized against one or more peptides restricted against an HLA-B7 allele.
11. The method of claim 10 , wherein said one or more peptides are selected from the list consisting of SEQ ID NO:45, SEQ ID NO:46, SEQ ID NO:47, SEQ ID NO:48, SEQ ID NO:49, SEQ ID NO:50, SEQ ID NO:51, SEQ ID NO:52, SEQ ID NO:53, SEQ ID NO:54, SEQ ID NO:55, SEQ ID NO:56, SEQ ID NO:57, or a combination thereof.
12. The method of claim 1 , wherein said COVID-19 peptide specific CTLs were sensitized against one or more peptides restricted against an HLA-B40 allele.
13. The method of claim 12 , wherein said one or more peptides selected from the list consisting of SEQ ID NO:58, SEQ ID NO:59, SEQ ID NO:60, SEQ ID NO:61, SEQ ID NO:62, SEQ ID NO:63, SEQ ID NO:64, SEQ ID NO:65, SEQ ID NO:66, SEQ ID NO:67, or a combination thereof.
14. The method of claim 1 , wherein said COVID-19 peptide specific CTLs were sensitized against one or more peptides restricted against an HLA-Cw7 allele.
15. The method of claim 1 , wherein said one or more peptides are selected from the list consisting of SEQ ID NO:68, SEQ ID NO:69, SEQ ID NO:70, SEQ ID NO:71, SEQ ID NO:72, SEQ ID NO:73, SEQ ID NO:74, SEQ ID NO:75, SEQ ID NO:76, SEQ ID NO:77, or a combination thereof.
16. The method of claim 1 , wherein said COVID-19 peptide specific CTLs were sensitized against a combination of COVID-19 peptides binding to any one or combination of HLA-A1, A2, B7, B40, Cw7 alleles.
17. A method of preparing COVID-19 peptide specific cytotoxic T cells (CTLs) that are specifically enriched cells reactive to COVID-19 peptide comprising:
a. a first stimulation step, whereby a subset of monocytes are treated to induce maturation into dendritic cells, the dendritic cells are pulsed with one or more COVID-19 specific peptides and co-cultured with lymphocytes for at least six days;
b. a second stimulation step, whereby monocytes are used to present the COVID-19 specific peptides, stimulated lymphocytes are cultured for at least seven days, peptide specific CTLs are selected due to preferential adherence of T cells recognizing the pulse peptides to an adherent monocyte layer; and
c. a third stimulation step, whereby a subset of monocytes are pulsed with multiple COVID-19 specific peptides restricted against a single HLA allele; thereby producing COVID-19 specific CTLs, wherein at least 20% of the CTLs are reactive to COVID-19 peptides.