Anti CD30 chimeric antigen receptor and its use
In a first aspect, the present disclosure relates to genetically modified T-cells having a chimeric antigen receptor for use in adoptive cell therapy for treating CD30+ cancer in a subject need thereof. In particular, the present disclosure relates to a T-cell containing a specific chimeric antigen receptor being toxic to CD30+cancer cells while being non-toxic to CD30+ non-cancer cells. In a further aspect, the present disclosure relates to a specific chimeric antigen receptor and the nucleic acid molecule encoding the receptor as well as vectors and cells containing the same. Finally, the present disclosure relates to the use of the chimeric antigen receptor for use in improving persistence and amplification of lymphocyte containing the same and the use of specific peptides for improving persistence and amplification of genetically modified lymphocytes expressing the same.
1. A method of adoptive cell therapy for treating CD30 + cancer in a subject in need thereof comprising the step of administering to said subject a T-cell with a chimeric antigen receptor whereby the chimeric antigen receptor contains at least the following domains starting from the N-terminus to the C-terminus:
an HRS3 scFv peptide having the sequence as set forth in SEQ ID No. 2,
optionally a spacer domain,
a transmembrane domain of CD28,
a cytoplasmic signaling domain, wherein the cytoplasmic signaling domain is selected from the CD3 zeta signaling domain of SEQ ID No. 7,
a Fc epsilon receptor gamma-signaling domain of SEQ ID No. 8 or a CD28 signaling domain,
wherein said T-cell with the chimeric antigen receptor is toxic to CD30 + cancer cells, while being non-toxic to CD30 + non-cancer activated T cells, B cells and/or stem cells in said subject, and wherein said CD30 + cancer cells include one or more of CD 30 + leukemia cells and CD30 + lymphoma cells.
2. The method for adoptive cell therapy for treating CD30 + cancer in a subject in need thereof according to claim 1 , wherein the T-cell with a chimeric antigen receptor further comprise a leader sequence located N-terminally to the anti-CD30 single chain antibody domain.
3. The method for adoptive cell therapy for treating CD30 + cancer in a subject in need thereof according to claim 1 wherein in the T-cell with a chimeric antigen receptor the spacer domain is an IgG1 CH2CH3 domain of SEQ. ID. No. 5 or homologs thereof having at least 70% identity therewith.
4. The method of claim 3 wherein the spacer domain is a mutated IgG 1 CH2CH3 domain according to SEQ. ID. No. 5.
5. The method for adoptive cell therapy for treating CD30 + cancer in a subject in need thereof according to claim 1 , wherein in the T-cell with a chimeric antigen receptor the chimeric antigen receptor is a polypeptide of SEQ. ID. No. 3.
6. The method for adoptive cell therapy for treating CD30 + cancer in a subject need thereof according to claim 1 wherein the CD30 + cancer is any one of Hodgkin's lymphoma, anaplastic large cell lymphoma, acute lymphocytic leukaemia, cutaneous lymphoma, mycosis fungoides, lymphoproliferative diseases, systemic mastocytosis, teratocarcinoma, stem cell derived malignancies, cancer stem cells.
7. The method of adoptive cell therapy for treating CD30 + cancer in a subject in need thereof according to claim 1 wherein the CD30 + cancer is selected from the group consisting of Hodgkin's lymphoma, non-Hodgkin's B cell lymphoma, mycosis fungoides or Sézary lymphoma.