Treatment of CD30-positive cancer
Methods for treating a CD30-positive cancer in a subject are disclosed, wherein the methods comprise administering a lymphodepleting chemotherapy and CD30-specific chimeric antigen receptor (CAR)-expressing cells.
1 . A method of treating a CD30-positive cancer in a subject, comprising:
(a) administering a lymphodepleting chemotherapy to the subject, and
(b) subsequently administering CD30-specific chimeric antigen receptor (CAR)-expressing T cells to the subject, wherein the CD30-specific CAR-expressing T cells comprise a CAR comprising:
(i) an antigen-binding domain which binds specifically to CD30,
(ii) a transmembrane domain, and
(iii) a signalling domain, wherein the signalling domain comprises an amino acid sequence derived from the intracellular domain of CD28, and an amino acid sequence comprising an immunoreceptor tyrosine-based activation motif (ITAM),
wherein the CAR comprises the amino acid sequence of SEQ ID NO:35 or 36; and
wherein the method has an objective response rate (ORR) of at least 75%.
2 . The method according to claim 1 , wherein administering a lymphodepleting chemotherapy to the subject comprises administering fludarabine and bendamustine.
3 . The method according to claim 1 , wherein the method comprises administering fludarabine at a dose of 15 to 60 mg/m 2 per day, for 2 to 6 consecutive days.
4 . The method according to claim 1 , wherein the method comprises administering fludarabine at a dose of 30 mg/m 2 per day, for 3 consecutive days.
5 . The method according to claim 1 , wherein the method comprises administering bendamustine at a dose of 35 to 140 mg/m 2 per day, for 2 to 6 consecutive days.
6 . The method according to claim 1 , wherein the method comprises administering bendamustine at a dose of 70 mg/m 2 per day, for 3 consecutive days.
7 . The method according to claim 1 , wherein the method comprises administering 5×10 7 CD30-specific CAR-expressing T cells/m 2 to 1×10 9 CD30-specific CAR-expressing T cells/m 2 to the subject.
8 . The method according to claim 1 , wherein the method comprises administering 1×10 8 CD30-specific CAR-expressing T cells/m 2 to 6×10 8 CD30-specific CAR-expressing T cells/m 2 to the subject.
9 . The method according to claim 1 , wherein the method comprises:
(i) administering fludarabine at a dose of 30 mg/m 2 per day and bendamustine at a dose of 70 mg/m 2 per day to a subject for 3 consecutive days, and
(ii) subsequently administering CD30-specific CAR-expressing T cells to the subject at a dose of 2×10 8 CD30-specific CAR-expressing T cells/m 2 to 6×10 8 CD30-specific CAR-expressing T cells/m 2 .
10 . The method according to claim 1 , wherein the CD30-positive cancer is selected from: a hematological cancer, a solid cancer, a hematopoietic malignancy, Hodgkin's lymphoma, anaplastic large cell lymphoma, peripheral T cell lymphoma, peripheral T cell lymphoma not otherwise specified, T cell leukemia, T cell lymphoma, cutaneous T cell lymphoma, NK-T cell lymphoma, extranodal NK-T cell lymphoma, non-Hodgkin's lymphoma, B cell non-Hodgkin's lymphoma, diffuse large B cell lymphoma, diffuse large B cell lymphoma not otherwise specified, EBV-positive B cell lymphoma, EBV-positive diffuse large B cell lymphoma, primary mediastinal B cell lymphoma, advanced systemic mastocytosis, a germ cell tumor and testicular embryonal carcinoma.
11 . The method according to claim 1 , wherein the subject has previously failed therapy for the CD30-positive cancer.
12 . The method according to claim 1 , wherein the CD30-positive cancer is a relapsed or refractory CD30-positive cancer.