METHODS AND COMPOSITIONS FOR DETECTING IMMUNE RESPONSES
Methods and compositions for detecting immune responses and antigen-specific cells are described herein.
1 .- 42 . (canceled)
43 . A method of evaluating treatment of a subject, the method comprising:
(a) obtaining a sample comprising hematopoietic cells from a subject of a first species, wherein the subject is undergoing or being evaluated for an immunotherapeutic treatment for a disease or condition;
(b) providing a target cell of a second species, wherein the second species is different from the first species, wherein the second species is a macaque species, wherein the target cell comprises an antigen, and wherein previous determination of the target cell MHC genotype is not required;
(c) contacting the target cell with the sample;
(d) detecting expression of an immune activation marker or activity in the sample, wherein an increase in expression of the immune activation marker or activity in the sample, relative to a control, is an indication that the sample comprises an antigen-specific hematopoietic cell; and wherein a cell essentially identical to the target cell but lacking the antigen does not stimulate expression of the immune activation marker or activity in hematopoietic cells of the first species, thereby evaluating treatment of the subject or evaluating the subject.
44 . The method of claim 43 , further comprising:
(e) transmitting the result from the detecting of step (d) to a caregiver.
45 . The method of claim 44 , wherein the caregiver evaluates a further treatment of the subject as a function of the result of the detecting of step (d).
46 . The method of claim 43 , wherein the macaque species is rhesus macaque.
47 . The method of claim 43 , wherein the target cell is the cell of a cell line.
48 . The method of claim 47 , wherein the cell line is an epithelial cell line.
49 . The method of claim 48 , wherein the epithelial cell line is a mammary epithelial cell line.
50 . The method of claim 49 , wherein the cell line is CMMT 110/C1.
51 . The method of claim 43 , wherein the antigen is a tumor-associated antigen (TAA) or a microbial antigen.
52 . The method of claim 51 , wherein the antigen is a carcinoembryonic antigen (CEA) or a mucin-1 (MUC-1).
53 . The method of claim 43 , wherein the sample comprises peripheral blood mononuclear cells (PBMC).
54 . The method of claim 43 , wherein the immune activation marker is selected from the group consisting of a cytokine, a chemokine, a cytotoxin, and a cell surface marker for activated hematopoietic cells.
55 . The method of claim 54 , wherein the immune activation marker is a cytokine selected from IFN-γ, TGF-β, TNF-α, TNF-β, GM-CSF, G-CSF, interleukin-2 (IL-2), IL-3, IL-4, IL-5, IL-6, IL-10, IL-12, and IL-15.
56 . The method of claim 54 , wherein the immune activation marker is a chemokine selected from CCL3/MIP-1α, MIP-1β, CCL5/RANTES, XCL1/lymphotactin, and CXCL10/IP-10.
57 . The method of claim 54 , wherein the immune activation marker is granzyme.
58 . The method of claim 54 , wherein the immune activation marker is a costimulatory molecule.
59 . The method of claim 54 , wherein the immune activation marker is selected from B7.1, B7.2, CD152 (CTLA-4), CD28, CD40, CD40 ligand (CD40L), and CD69.
60 . The method of claim 43 , wherein the immune activation activity is proliferation of the hematopoietic cells or lysis of target cells.
62 . The method of claim 43 , wherein the target cell is infected with a virus that encodes the antigen.
63 . The method of claim 62 , wherein the virus is a DNA virus or a poxvirus.