Methods of selecting T cell line and donor thereof for adoptive cellular therapy
Disclosed herein are methods of selecting an allogeneic T cell line for therapeutic administration to a patient having or suspected of having a pathogen or cancer. Also disclosed are methods of selecting a donor from whom to derive an allogeneic T cell line for therapeutic administration to a patient having or suspected of having a pathogen or cancer.
1. A method of selecting an allogeneic T cell line for therapeutic administration to a human patient having or suspected of having a pathogen or cancer, comprising:
(a) selecting a T cell line allogeneic to the patient that recognizes at least one epitope of an antigen of the pathogen or the cancer, using a representation that (i) identifies a plurality of HLA alleles and optionally HLA allele combinations, and (ii) discloses indications of relative activities of T cell lines, each recognizing at least one epitope of an antigen of the pathogen or cancer, and restricted to different ones of the HLA alleles or HLA allele combinations in the plurality; wherein in the representation each identified HLA allele or HLA allele combination is associated with the respective indication of relative activity of the T cell line restricted to the HLA allele or HLA allele combination, the relative activities being relative measures of known activity against the pathogen or against the cancer exhibited by the T cell lines, wherein the relative activities are in vivo clinical efficacies of the T cell lines in treatment of human patients having the pathogen or cancer, wherein each indication of relative activity is based on clinical data from a population of human patients; wherein
(A) the T cell line selected has in common with the patient or diseased cells in the patient the HLA allele or HLA allele combination identified by the representation to which the recognition of the T cell line is restricted; and
(B) the HLA allele or HLA allele combination, to which the T cell line selected is restricted, is associated in the representation with an indication of the highest relative activity among the HLA alleles and HLA allele combinations in the representation that are known to be in common with the patient or the diseased cells in the patient and are not otherwise disqualified;
(b) generating the representation prior to the selecting step; and
(c) measuring the relative activities prior to the generating step.
2. The method of claim 1 , wherein the representation is a list of the plurality of HLA alleles and optionally HLA allele combinations ranked by the relative activities.
3. The method of claim 1 , wherein the representation is a database listing the plurality of HLA alleles and optionally HLA allele combinations, each associated with a score indicative of relative activity.
4. The method of claim 1 , wherein the patient has or is suspected of having a pathogen, wherein the T cell lines recognize at least one epitope of an antigen of the pathogen, and wherein the relative activities are relative measures of known activity against the pathogen.
5. The method of claim 4 , wherein the pathogen is a virus.
6. The method of claim 5 , wherein the virus is CMV.
7. The method of claim 6 , wherein the patient has or is suspected of having a CMV infection subsequent to the patient having undergone a hematopoietic stem cell transplant.
8. The method of claim 6 , wherein the antigen is CMV pp65.
9. The method of claim 5 , wherein the virus is EBV.
10. The method of claim 1 , wherein the patient has or is suspected of having a cancer, wherein the T cell line recognizes at least one epitope of an antigen of the cancer, and wherein the relative activities are relative measures of known activity against the cancer.
11. The method of claim 10 , wherein the antigen is WT1.
12. The method of claim 10 , wherein the cancer is a lymphoproliferative disorder.
13. The method of claim 12 , wherein the cancer is an EBV-positive post-transplant lymphoproliferative disorder.
14. The method of claim 13 , wherein the antigen is EBNA1, EBNA2, EBNA3A, EBNA3B, EBNA3C, LMP1 or LMP2.
15. The method of claim 10 , wherein the cancer is an EBV-positive nasopharyngeal carcinoma.
16. The method of claim 15 , wherein the antigen is EBNA1, LMP1, or LMP2.
17. The method of claim 10 , wherein the cancer is a cancer of the blood, breast, lung, ovary, stomach, pancreas, larynx, esophagus, testes, liver, parotid, biliary tract, colon, rectum, cervix, uterus, endometrium, kidney, bladder, prostate, thyroid, brain or skin.