Use of triplex CMV vaccine in CAR T cell therapy

Patent metadata

Field	Value
Publication number	US-12478672-B2
Application number	US-202318354849-A
Country	US
Kind code	B2
Filing date	Jul 19, 2023
Priority date	Oct 19, 2016
Publication date	Nov 25, 2025
Grant date	Nov 25, 2025

Abstract

A method for treating a patient comprising: (a) providing a composition comprising a population of T cells expressing both a chimeric antigen receptor (CAR) and a T cell receptor specific for a cytomegalovirus (CMV) antigen; (b) administering the composition to the patient; and (c) administering to the patient a viral vector encoding: (i) CMV pp65 and (ii) a fusion protein comprising exon 4 of CMV protein IE1 (e4) and exon 5 of CMV protein IE2 (e5) either prior to or subsequent to administering the composition comprising a population of T cells to the patient is described.

First claim

What is claimed is:

1 . A method for treating a patient suffering from lymphoma expressing CD19 comprising:
(a) providing a composition comprising a population of T cells expressing both a chimeric antigen receptor (CAR) targeted to CD19 and a T cell receptor that binds a cytomegalovirus (CMV) antigen pp65; (b) administering the composition of part (a) to the patient; and (c) administering to the patient a viral vector encoding:
(i) CMV pp65 and
(ii) a fusion protein comprising exon 4 of CMV protein IE1 (e4) and exon 5 of CMV protein IE2 (e5).

2 . The method of claim 1 , wherein the viral vector of part (c) is a MVA virus.

3 . The method of claim 2 , wherein expression of (i) CMV pp65 and (ii) the fusion protein comprising exon 4 of CMV protein IE1 (e4) and exon 5 of CMV protein IE2 (e5) is under the control of mH5 promoter.

4 . The method of claim 1 , wherein the patient is CMV-seronegative prior to treatment.

5 . The method of claim 1 , wherein the patient is CMV-seropositive prior to treatment.

6 . The method of claim 1 , wherein the viral vector is administered to the patient both prior to and subsequent to the administration of the composition comprising a population of T cells.

7 . The method of claim 1 , wherein the step of providing a population of T cells expressing a CAR and a T cell receptor that binds a CMV antigen comprises:
(a1) providing PBMC or a T cell subpopulation from a CMV-seropositive human donor; (a2) exposing the PBMC or the T cell subpopulation of part (a1) to at least one CMV antigen; (a3) treating the exposed cells of part (a2) to produce a population of cells enriched for cells expressing a T cell receptor that bind a CMV antigen; and (a4) transducing at least a portion of the enriched population of cells of part (a3) with a vector expressing a CAR.

8 . The method of claim 7 , wherein the step of treating the exposed cells to produce a population of cells enriched for cells expressing a T cell receptor that binds a CMV antigen comprises treating the cells to produce a population of cells enriched for cells expressing an activation marker.

9 . The method of claim 1 , wherein the step of providing a population of T cell expressing a CAR and a T cell receptor that binds a CMV antigen further comprises:
(a1) administering a viral vector encoding: (i) CMV pp65 and (ii) a fusion protein comprising exon 4 of CMV protein IE1 (e4) and exon 5 of CMV protein IE2 (e5) to a human donor to convert a CMV-seronegative human donor to one containing T cells responsive to CMV antigens pp65, IE1 and IE2; (a2) obtaining PBMC from the CMV-seropositive human donor of (a1); (a3) exposing the PBMC of (a2) to at least one CMV antigen; (a4) treating the exposed cells of (a3) to produce a population of cells enriched for stimulated cells expressing a T cell receptor that binds a CMV antigen; and (a5) transducing at least a portion of the enriched population of cells of (a4) with a vector expressing a CAR, thereby providing a population of T cell expressing a CAR and a T cell receptor that binds a CMV antigen.

10 . The method of claim 1 , wherein the step of providing a population of T cell expressing a CAR and a T cell receptor that binds a CMV antigen comprises:
(a1) administering a viral vector encoding: (i) CMV pp65 and (ii) a fusion protein comprising exon 4 of CMV protein IE1 (e4) and exon 5 of CMV protein IE2 (e5) to a CMV-positive human donor; (a2) obtaining PBMC from the CMV-seropositive human donor of (a1); (a3) exposing the PBMC of (a2) to at least one CMV antigen; (a4) treating the exposed cells of (a3) to produce a population of cells enriched for stimulated cells expressing a T cell receptor that binds a CMV antigen; (a5) transducing at least a portion of the enriched population of cells of (a4) with a vector expressing a CAR, thereby providing a population of T cell expressing a CAR and a T cell receptor that binds a CMV antigen.

Assignees

• Hope City

Inventors

• Diamond Don J
• Wang Xiuli
• Forman Stephen J

Classifications

• C12N5/0636

  T lymphocytes · CPC title

• C07K2319/33

  fusions for targeting to specific cell types, e.g. tissue specific targeting, targeting of a bacterial subspecies · CPC title

• C07K2319/03

  containing a transmembrane segment · CPC title

• C07K16/2803

  against the immunoglobulin superfamily · CPC title

• C07K14/70578

  NGF-receptor/TNF-receptor superfamily, e.g. CD27, CD30, CD40, CD95 (NGF-receptor C07K14/71, TNF-receptor C07K14/7151) · CPC title