Chimeric antigen receptors (car)-expressing cells and combination treatment for immunotherapy of patients with relapse refractory adverse genetic risk aml
OwnerStéphane André DEPIL, Ghulam MUFTI +1inventors
InventorsStéphane André DEPIL, Ghulam MUFTI, David SOURDIVE
Life of this patent
Estimating the term…
Abstract
The present invention relates to compositions comprising engineered allogenic immune cells endowed with Chimeric Antigen Receptors (CAR), in particular a CAR specific for CD123 and CLL1 for treating AML patients with adverse genetic risk.
Claims25
A method for treating a patient having an adverse genetic risk of AML by cell immunotherapy, said method comprising:
- i) subjecting the patient to induction chemotherapy treatment to reduce blasts in bone marrow of the patient to lower than 20%;
- wherein minimal residual disease (MRD) is not achieved;
- ii) subjecting the patient to lymphodepleting treatment to reduce the patient's own immune cells;
- iii) subjecting the patient to immunotherapy treatment comprising administering a dose of engineered immune cells expressing a chimeric antigen receptor (CAR) or a recombinant TCR specific for a tumoral antigen marker at the surface membrane of said remaining blasts to achieve MRD;
- and
- iv) optionally, administering a second dose of engineered immune cells expressing a chimeric antigen receptor (CAR) until reaching actual MRD;
- v) optionally, treating the patient with a pre-conditioning regimen prior to bone marrow transplant;
- and/or
- vi) optionally, proceeding to a bone marrow transplant.
(canceled)
14-15. (canceled)
A method for achieving remission of a hematological cancer in a patient comprising:
- a) identifying a patient with a hematological cancer with adverse cytogenetic risk;
- b) measuring blasts content over total cells in a sample of the bone marrow of said patient;
- wherein if blast content is less than 20% over total cells in the bone marrow step (d) is performed;
- c) wherein if blast content is more than 20% over total cells in the bone marrow, at least one debulking treatment(s) is administered to reach less than 20% blasts in the bone marrow;
- d) lymphodepleting said patient and administering one dose of engineered immune cells expressing a CAR specific for a tumoral antigen marker at the cell surface membrane of said remaining blasts;
- and
- e) measuring blasts in the bone marrow;
A method for monitoring a patient being treated for adverse genetic risk AML using engineered CAR positive immune cells and a plurality of stem cells, wherein said method comprises the steps of:
- a) vivo analyzing, ex vivo, blasts from the patient's bone marrow sample, said patient having been pre-treated by induction chemotherapy;
- b) wherein if blast count is between 1 and 20% in the sample, the method comprises preparing ex-vivo engineered CAR positive immune cells directed against an antigen marker present on said blasts;
- c) optionally, two weeks after treating the patient with the engineered CAR positive immune cells, analyzing the blasts ex vivo from patient's bone marrow sample by flow cytometry to determine whether MRD is reached if not, the method further comprises providing ex-vivo engineered CAR positive immune cells of step b) in view of a second round of treatment;
- d) optionally, if MRD is reached in step c), the method comprises providing stem cells from a compatible donor in view of a transplant.
24-37. (canceled)
A medical kit comprising at least a first and second composition for sequential use for treating AML, wherein said first composition is used for induction chemotherapy to reduce or maintain blasts in bone marrow between 1 and 20%, and wherein said second composition comprises a dose of engineered immune cells expressing a chimeric antigen receptor (CAR) specific for a tumoral antigen at the cell surface membrane.
Dependencies are inferred from the claim text.