Table 5.
Adoptive cellular therapies used to treat AML patients in clinical trial.
| Cell Type | Ag Targeted | Manufacturing Method | Pt. n |
Disease Status | Treatment Associated Toxicities | Disease Outcome | Notes | Clinical Trial No./ (Reference) |
|---|---|---|---|---|---|---|---|---|
| CAR-T cells | CD33 | -Autologous T cell source - Lenti-virally transduced - CD3ζ and 4-1BB intracellular domain -T cells were cultured in the presence of CD3 antibody, IL-2 and IFNγ for 11 days. |
1 | Relapsed | Grade 4 chills Exacerbation of existing pancytopenia |
-BM blasts decreased from >50% to <6% @ 2wks -70% BM blasts @ 9wks |
-CD33-CART persisted and retained anti-leukemic activity ex vivo -Blasts developed resistance to CD33-CART cells |
NCT01864902 [82] |
| CAR T cell | CLL-1 | -Autologous T cell source -Lenti-virally transduced - Fourth generation CLL- CAR containing CD3, CD28, and CD27 intracellular domain. |
1 | Secondary AML | Grade I/II CRS developed. Patient experienced hypotension | -MRD negative -Morphological CR |
-CR retained up to 10 months. -A low CAR T-cell level persistence was detected 5 months after CAR T-cell injection |
trial number not available. [83] |
| CAR T cell | CD33 and CLL-1 | -Autologous T cell source - Anti-CLL1/CD33 CAR linked via a self-cleaving P2A peptide. |
2 | Refractory /relapsed |
Pancytopenia | -MRD negative CR for both patients | -An alemtuzumab safety switch implemented to eliminate CAR T cells following tumor eradication. |
NCT03795779 [84,85] |
| CAR T cell | CD123 | -Autologous T cell source -Lenti-virally transduced - CD3 and CD28 intracellular domain |
6 | Refractory AML after allo-HSCT | Grade 1 or 2 CRS reported in most patients, but did not reach dose-limiting toxicities. | Morphological CR (n = 1) CR (n = 2) Partial response (n = 2) |
-CR patients received secondary allo-HSCT |
NCT02159495 [86] |
| NK-92 | Unspecified | -Allogeneic NK source -Expanded in presence of IL-2 -Ex vivo expanded NK-92 cells were irradiated at 1,000 cGy prior to patinet infusion |
7 | Refractory/ Relapsed |
No AE | -PD (n = 3) -Decreased BM blasts (n = 1) -Stable % BM blasts (n = 2) -NE (n = 1) |
-2-6 infusions given per patient |
NCT00900809 [87] |
| CIML NK cell | Unspecified | -Allogeneic NK cell source -Pre-activated with IL-12, IL-15, and IL-18. -Subsequently, cultured in the presence of IL-2 |
9 | Refractory/ Relapsed |
No AE | -CR/CRi (n = 4) -Morpohlogical CR (n = 1) |
-13 patients enrollled. 4 were inevaluable due to manufacturing failure, death before evaluation of responses. |
NCT01898793 [88] |
| DNT cell | Unspecified | -Allogeneic T cell source -CD3+ CD4- CD8- cells expanded in the presence of anti-CD3 antibody and IL-2 |
12 | Relapsed after allo-HSCT | Grade I/II CRS | -CR/CRi (n = 6) -Partial remission (n = 1) |
-1 patient withdrew from the study | ChiCTR-IPR-1900022795 [89] |
AML = acute myeloid leukemia; NK = natural killer; AE = adverse events; CR = complete remission; NE = not evaluable; alloHSCT = allogeneic hematopoietic stem cell transplant; MRD = minimal residual disease; aNK = activated NK cells; PD = progressive disease.