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Hieh-Dose Immunosuppressive Chemotherapy with Autologous Stem Cell Support for Chronic Autoimmune Thrombocytopenia
Published in Richard K. Burt, Alberto M. Marmont, Stem Cell Therapy for Autoimmune Disease, 2019
Richard D. Huhn, Patrick F. Fogarty, Ryotaro Nakamura, Cynthia E. Dunbar
The availability of precise quantitative assays for anti-platelet T-lymphocytes would enable mechanistically significant studies of important immune parameters. Such assays could be based on the so-called tetramer assay in which T-lymphocytes having receptors for specific antigens can be detected by flow cytometry after they bind peptides that secondarily bind fluorochrome-linked avidin-biotin complexes.61 Alternatively, flow cytometric detection of intracellular cytokine production by T lymphocytes exposed to autoantigens (the so-called Fastimmune™ assay) could be used in a similar manner.62,63 It would also be of significant interest to monitor the depletion of autoreactive lymphocytes from blood stem cell grafts using such assays and to attempt to examine associations between relative depletion and clinical responses.
Combining therapeutic vaccines with chemo- and immunotherapies in the treatment of cancer
Published in Expert Opinion on Drug Discovery, 2021
Matthew D. Kerr, David A. McBride, Arun K. Chumber, Nisarg J. Shah
Similar to oncofetal mutations, germline/cancer testis mutations may be upregulated by cancer cells and is generally restricted to immune-privileged germline cells. Common therapeutic vaccine target mutations include Wilms tumor 1 (WT1) protein, melanoma-associated antigen (MAGE) superfamily, and cancer/testis antigen 1 (NY-ESO-1). A National Cancer Institute consensus study on prioritization of cancer antigens ranked the WT1 protein as the top immunotherapy target in cancer, which is overexpressed on multiple tumor types, including acute myeloid leukemia [64,65]. A multivalent WT1 peptide vaccine (galinpepimut-S) has been developed and tested in acute myeloid leukemia (AML) patients in phase 1 and 2 clinical trials [66]. In the most recent phase 2 trial (NCT01266083), patients in complete remission received six vaccinations administered over 10 weeks with the potential to receive 6 additional monthly doses if they remained in remission. Immune responses (IRs) were evaluated after the 6th and 12th vaccinations by CD4+ T cell proliferation, CD8+ T cell IFN-γ secretion, or the CD8-relevant WT1 peptide major histocompatibility complex tetramer assay. In terms of compliance, 14 patients (64%) completed ≥6 vaccinations, and only 9 (41%) received all 12 vaccine doses. Fifteen patients (68%) relapsed, and 10 (46%) died. The vaccine was well tolerated, with the most common toxicities being grade 1/2 injection site reactions (46%), fatigue (32%), and skin induration (32%). Median disease-free survival from first complete remission was 16.9 months, whereas the overall survival from diagnosis was estimated to be ≥5 years. Nine of 14 tested patients (64%) had an IR in ≥1 assay (CD4 or CD8) [66].