US 12,403,185 B2
Use of anti-CD137 antibody drug conjugate (ADC) in allogeneic cell therapy
Anthony Boitano, Newton, MA (US); and Michael Cooke, Boston, MA (US)
Assigned to Heidelberg Pharma Research GmbH, Ladenburg (DE)
Filed by Heidelberg Pharma Research GmbH, Ladenburg (DE)
Filed on Jan. 22, 2021, as Appl. No. 17/155,936.
Application 17/155,936 is a continuation of application No. PCT/US2019/043119, filed on Jul. 23, 2019.
Claims priority of provisional application 62/702,292, filed on Jul. 23, 2018.
Prior Publication US 2021/0228696 A1, Jul. 29, 2021
This patent is subject to a terminal disclaimer.
Int. Cl. A61K 39/00 (2006.01); A61K 38/07 (2006.01); A61K 38/12 (2006.01); A61K 40/11 (2025.01); A61K 40/31 (2025.01); A61K 40/41 (2025.01); A61K 40/50 (2025.01); A61K 47/64 (2017.01); A61K 47/65 (2017.01); A61K 47/68 (2017.01); A61P 37/06 (2006.01)
CPC A61K 39/001 (2013.01) [A61K 38/07 (2013.01); A61K 38/12 (2013.01); A61K 40/11 (2025.01); A61K 40/31 (2025.01); A61K 40/418 (2025.01); A61K 47/6415 (2017.08); A61K 47/65 (2017.08); A61K 47/6831 (2017.08); A61K 47/6849 (2017.08); A61P 37/06 (2018.01); A61K 40/50 (2025.01); A61K 2239/31 (2023.05); A61K 2239/38 (2023.05)] 23 Claims
 
1. A method for treating or reducing rai versus host disease of allogeneic cells transplanted into a human subject, the method comprising
(a) administering to the human subject a first amount of an allogeneic cell, wherein
the first amount is sufficient to elicit a priming response to the allogeneic cell in the human subject;
(b) administering an anti-CD 137 antibody drug conjugate (ADC) to the human subject such that endogenous CD137+ activated T cells are depleted, wherein the anti-CD137 ADC comprises an anti-CD137 antibody, or antigen-binding fragment thereof, conjugated to a cytotoxin via a linker; and
(c) administering a therapeutically effective amount of an allogeneic cell expressing a CAR to the human subject, wherein the allogeneic cell is the same type of allogeneic cell administered in (a), and wherein the CAR comprises an extracellular domain that binds to a tumor antigen, a transmembrane domain, and a cytoplasmic signaling domain;
wherein the cytotoxin is an RNA polymerase inhibitor, and
wherein the RNA polymerase inhibitor is an amanitin selected from the group consisting of α-amanitin, β-amanitin, γ-amanitin, ε-amanitin, amanin, amaninamide, amanullin, amanullinic acid, and proamanullin.