The graft-versus-leukemia effect of allogeneic hematopoietic stem cell transplantation (HSCT) has shown that the immune system is capable of eradicating acute myeloid leukemia (AML). This knowledge, ...along with the identification of the target antigens against which antileukemia immune responses are directed, has provided a strong impetus for the development of antigen-targeted immunotherapy of AML. The success of any antigen-specific immunotherapeutic strategy depends critically on the choice of target antigen. Ideal molecules for immune targeting in AML are those that are: (1) leukemia-specific; (2) expressed in most leukemic blasts including leukemic stem cells; (3) important for the leukemic phenotype; (4) immunogenic; and (5) clinically effective. In this review, we provide a comprehensive overview on AML-related tumor antigens and assess their applicability for immunotherapy against the five criteria outlined above. In this way, we aim to facilitate the selection of appropriate target antigens, a task that has become increasingly challenging given the large number of antigens identified and the rapid pace at which new targets are being discovered. The information provided in this review is intended to guide the rational design of future antigen-specific immunotherapy trials, which will hopefully lead to new antileukemia therapies with more selectivity and higher efficacy.
Cancer patients are at a higher risk of developing severe coronavirus disease 2019 (COVID-19). However, the safety and efficacy of COVID-19 vaccination in cancer patients undergoing treatment remain ...unclear.
In this interventional prospective multicohort study, priming and booster doses of the BNT162b2 COVID-19 vaccine were administered 21 days apart to solid tumor patients receiving chemotherapy, immunotherapy, targeted or hormonal therapy, and patients with a hematologic malignancy receiving rituximab or after allogeneic hematopoietic stem cell transplantation. Vaccine safety and efficacy (until 3 months post-booster) were assessed. Anti-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) receptor-binding domain (RBD) antibody levels were followed over time (until 28 days after the booster) and in vitro SARS-CoV-2 50% neutralization titers (NT50) toward the wild-type Wuhan strain were analyzed 28 days after the booster.
Local and systemic adverse events (AEs) were mostly mild to moderate (only 1%-3% of patients experienced severe AEs). Local, but not systemic, AEs occurred more frequently after the booster dose. Twenty-eight days after the booster vaccination of 197 cancer patients, RBD-binding antibody titers and NT50 were lower in the chemotherapy group {234.05 IU/ml 95% confidence interval (CI) 122.10-448.66 and 24.54 (95% CI 14.50-41.52), respectively} compared with healthy individuals 1844.93 IU/ml (95% CI 1383.57-2460.14) and 122.63 (95% CI 76.85-195.67), respectively, irrespective of timing of vaccination during chemotherapy cycles. Extremely low antibody responses were seen in hematology patients receiving rituximab; only two patients had RBD-binding antibody titers necessary for 50% protection against symptomatic SARS-CoV-2 infection (<200 IU/ml) and only one had NT50 above the limit of detection. During the study period, five cancer patients tested positive for SARS-CoV-2 infection, including a case of severe COVID-19 in a patient receiving rituximab, resulting in a 2-week hospital admission.
The BNT162b2 vaccine is well-tolerated in cancer patients under active treatment. However, the antibody response of immunized cancer patients was delayed and diminished, mainly in patients receiving chemotherapy or rituximab, resulting in breakthrough infections.
•The BNT162b2 vaccine is well-tolerated in cancer patients, including patients under immunotherapy.•Full BNT162b2 vaccination results in a blunted humoral immune response in cancer patients under active treatment.•The humoral immune response after BNT162b2 vaccination varies between different antineoplastic treatments.•Two doses of BNT162b2 vaccination may insufficiently protect patients receiving chemotherapy or rituximab against SARS-CoV-2.
Interferon-α (IFN-α), a type I IFN, is a well-known antitumoral agent. The investigation of its clinical properties in acute myeloid leukemia (AML) has been prompted by its pleiotropic ...antiproliferative and immune effects. So far, integration of IFN-α in the therapeutic arsenal against AML has been modest in view of the divergent results of clinical trials. Recent insights into the key pharmacokinetic determinants of the clinical efficacy of IFN along with advances in its pharmaceutical formulation, have sparked renewed interest in its use. This paper reviews the possible applicability of IFN-α in the treatment of AML and provides a rational basis to re-explore its efficacy in clinical trials.
Background & AimDendritic cells (DC) have the capacity to induce potent tumor antigen-specific T-cell immunity. We have completed vaccination in the adjuvant setting in 77 cancer patients (acute ...myeloid leukemia (AML, n=30), metastatic breast cancer (MBC, n=12), glioblastoma multiforme (GBM, n=13), malignant pleural mesothelioma (MPM, n=10) and other solid tumors (n=12)) with autologous DC electroporated with mRNA encoding the nearly universal tumor-associated antigen Wilms’ tumor 1 protein (WT1).Methods, Results & ConclusionWT1-targeted DC vaccination was feasible and safe in all patients. The majority of the patients showed a positive delayed type hypersensitivity (DTH) response to the vaccine. Objective clinical responses were observed among all tumor types, including complete (CR) and/or molecular remissions or stable disease (SD) in the AML group, partial responses (PR) and SD in the GBM group and SD in the MBC and MPM groups.In AML patients in first CR, median overall survival (OS) calculated from time of diagnosis was 56.1 months (mo). Median OS from time of diagnosis of metastasis was 41.9 mo in MBC, 43.7 mo from diagnosis in GBM and 35.7 mo from start of therapy in MPM; this compares favorably to numbers reported in the literature, respectively 24.8 mo, 14.7 mo and 22 mo.In AML, long-term OS was correlated with WT1-specific polyfunctional CD8 + T-cells in the DTH reaction sites and long-term CR with polyepitope WT1-specific tetramer+ CD8+ T-lymphocytes. In solid tumors, PR or SD was correlated with interferon (IFN)-gamma+ and/or tumor necrosis factor (TNF)-alpha+ WT1-specific CD4+ and/or CD8+ T-cells; increased OS in the GBM+MPM cohorts was correlated with IFN-gamma+ WT1-specific CD4+ T-lymphocytes. In conclusion, WT1-targeted DC vaccination is feasible, safe and immunogenic, and displays relevant anti-tumor activity in patients with hematological and solid malignancies. Most importantly, this treatment modality can confer a significant survival benefit to the patients.
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