Minor histocompatibility antigen-specific T cells with multiple distinct specificities can be isolated by direct cloning of IFNγ-secreting T cells from patients with relapsed leukemia responding to donor lymphocyte infusion

Identification of human minor histocompatibility antigens based on genetic association with highly parallel genotyping of pooled DNA

“…7,34 Indeed, CTLs specific for ACC-2, an HLA-B44-restricted minor H antigen restricted by the third exonic SNP on BCL2A1, 7 was independently isolated from the peripheral blood of a patient with recurrent leukemia re-entering complete remission after donor lymphocyte infusion. 32 The number of eligible allo-HSCT recipients has now been effectively doubled, accounting for 50% of transplants with HLA-A24 or 20% of all transplantations performed in the Asian population. In conclusion, we have described a simple but powerful method for minor H mapping to efficiently accelerate the discovery of novel minor H antigens that will be needed to contribute to our understanding of the molecular mechanism of human allo-immunity.…”

“…In fact, substantial numbers of CTL clones have been established worldwide and could serve as the probes to identify novel minor H antigens. 32,33 Once constructed, a panel of B-LCLs, including those transduced with HLA cDNAs, could be commonly applied to immunophenotyping with different CTL clones, especially when Finally, the discovery of ACC-1 C as a novel minor H antigen indicates that all the mismatched transplants at this locus could be eligible for allo-immune therapies, since we have previously demonstrated that the counter allele also encodes a minor H antigen, ACC-1 Y , which is preferentially expressed and presented on blood components including leukemic cells and may serve as a target of allo-immunity. 7,34 Indeed, CTLs specific for ACC-2, an HLA-B44-restricted minor H antigen restricted by the third exonic SNP on BCL2A1, 7 was independently isolated from the peripheral blood of a patient with recurrent leukemia re-entering complete remission after donor lymphocyte infusion.…”

Molecular persistence of chronic myeloid leukemia caused by donor T cells specific for lineage-restricted maturation antigens not recognizing immature progenitor-cells

“…In post transplantation patients with adequate responses to DLI for relapsed CML, we illustrated the correlation between the presence in vivo of T cells recognizing CML progenitor cells and complete remissions. 21,24,26,27 As malignant disease can only be maintained by leukemic stem cells with self-renewal capabilities, 28,29 it can be hypothesized that for definite control of malignant disease, an immune response against leukemic progenitor cells is needed. Cancer stem cells have been demonstrated not only in CML, but also in acute leukemia, myelodysplasia and breast cancer.…”

“…Previously, we have shown that this method allows the characterization of the complexity of tumor-reactive T cell responses in HLA-identical patient-donor combinations. 21,26 From this DLI refractory patient, we isolated two different HLA-B57-restricted T-cell clones and two different HLA-Cw6-restricted T-cell clones. Using the 51 Cr-release assay, we showed that these clones were cytolytic against EBV-LCL of the patient, but not the donor, indicating recognition of mHags.…”

Failure is not fatal: long-term remission in refractory acute myeloid leukemia (AML) after graft failure of cord blood stem cells

“…Several studies have shown a correlation between the presence of T cells recognizing leukemia CD34 þ progenitor cells and the occurrence of complete remissions in vivo. 7 Furthermore, distinct minor histocompatibility antigens expressed on AML progenitor cells, which are recognized by CD8 þ T cells, are emerging, and have been proposed as target antigens for immunotherapy. 8 In summary, we report the fascinating case of a primary refractory AML patient who achieved complete remission after an allogeneic SCT with graft failure, lasting now for more than 16 months.…”