Association of active immunotherapy with outcomes in cancer patients with COVID-19: a systematic review and meta-analysis.

BACKGROUND: During the COVID-19 pandemic, there are growing concerns about the safety of administering immunotherapy in cancer patients with COVID-19. However, current clinical guidelines provided no clear recommendation. METHODS: Studies were searched and retrieved from electronic databases. The meta-analysis was performed by employing the generic inverse-variance method. A random-effects model was used to calculate the unadjusted odds ratios (ORs) and adjusted ORs with the corresponding 95% CIs. RESULTS: This meta-analysis included 20 articles with 6,042 cancer patients diagnosed with COVID-19. According to the univariate analysis, the acceptance of immunotherapy within 30 days before COVID-19 diagnosis did not increase the mortality of cancer patients (OR: 0.92; 95% CI: 0.68-1.25; P=0.61). Moreover, after adjusting for confounders, the adjusted OR for mortality was 0.51, with borderline significance (95% CI: 0.25-1.01; P=0.053). Similarly, the univariate analysis showed that the acceptance of immunotherapy within 30 days before COVID-19 diagnosis did not increase the risk of severe/critical disease in cancer patients (OR: 1.07; 95% CI: 0.78-1.47; P=0.66). No significant between-study heterogeneity was found in these analyses. CONCLUSIONS: Accepting immunotherapy within 30 days before the diagnosis of COVID-19 was not significantly associated with a higher risk of mortality or severe/critical disease of infected cancer patients. Further prospectively designed studies with large sample sizes are required to evaluate the present results.

Inusual evolución de artritis reactiva tras inmunoterapia endovesical con BCG / Unusual evolution of reactive arthritis after endovesical immunotherapy with BCG

La instilación intravesical de BCG (Bacilo de Calmette-Guerin) es una terapia preparada con cepas debilitadas de Mycobacterium bovis y constituye un tratamiento complementario eficaz para el cáncer de vejiga superficial (no musculoinfiltrante o no invasivo) de alto riesgo. Aunque la seguridad para su uso clínico es alta, la inmunoterapia endovesical no está exenta de complicaciones. La artralgia y la artritis son complicaciones infrecuentes, pero potencialmente severas, cuyo diagnóstico temprano puede permitir un tratamiento médico adecuado y evitar la cronificación de la patología. El presente caso muestra el manejo terapéutico de la artrosis coxofemoral en una mujer de 59 años, una complicación grave e infrecuente, secundaria a una patología poco común como la artritis reactiva debida a la instilación de BCG

Intravesical instillation of BCG (Bacille Calmette-Guerin) is a therapy prepared with weakened strains of Mycobacterium bovis and is an effective complementary treatment for high-risk (non-musculoinfiltrating or non-invasive) bladder cancer. Although its safety for clinical use is high, endovesical immunotherapy is not without complications. Arthralgia and arthritis are infrequent, but potentially severe, complications, the early diagnosis of which can allow adequate medical treatment and avoid chronification of the pathology. This case shows the therapeutic management of hip osteoarthritis in a 59-year-old woman, a rare and serious complication, secondary to a rare pathology such as reactive arthritis due to BCG instillation

Treatment-induced lesions in newly diagnosed glioblastoma patients undergoing chemoradiotherapy and heat-shock protein vaccine therapy.

OBJECTIVES: Treatment-induced lesions represent a great challenge in neuro-oncology. The aims of this study were (i) to characterize treatment induced lesions in glioblastoma patients treated with chemoradiotherapy and heat-shock protein (HSP) vaccine and (ii) to evaluate the diagnostic accuracy of diffusion weighted imaging for differentiation between treatment-induced lesions and tumor progression. METHODS: Twenty-seven patients with newly diagnosed glioblastoma treated with HSP vaccine and chemoradiotherapy were included. Serial magnetic resonance imaging evaluation was performed to detect treatment-induced lesions and assess their growth. Quantitative analysis of the apparent diffusion coefficient (ADC) was performed to discriminate treatment-induced lesions from tumor progression. Mann-Whitney U-test and receiver operating characteristic (ROC) curves were used for analysis. RESULTS: Thirty-three percent of patients developed treatment-induced lesions. Five treatment-related lesions appeared between end of radiotherapy and the first vaccine administration; 4 lesions within the first 4 months from vaccine initiation and 1 at 3.5 years. Three patients with pathology proven treatment-induced lesions showed a biphasic growth pattern progressed shortly after. ADC ratio between the peripheral enhancing rim and central necrosis showed an accuracy of 0.84 (95% CI 0.63-1) for differentiation between progression and treatment-induced lesions. CONCLUSION: Our findings do not support the iRANO recommendation of a 6-month time window in which progressive disease should not be declared after immunotherapy initiation. A biphasic growth pattern of pathologically proven treatment-induced lesions was associated with a dismal prognosis. The presence of lower ADC values in the central necrotic portion of the lesions compared to the enhancing rim shows high specificity for detection of treatment-induced lesions.

FUNDAMANT: an interventional 72-week phase 1 follow-up study of AADvac1, an active immunotherapy against tau protein pathology in Alzheimer's disease.

BACKGROUND: Neurofibrillary pathology composed of tau protein is closely correlated with severity and phenotype of cognitive impairment in patients with Alzheimer's disease and non-Alzheimer's tauopathies. Targeting pathological tau proteins via immunotherapy is a promising strategy for disease-modifying treatment of Alzheimer's disease. Previously, we reported a 24-week phase 1 trial on the active vaccine AADvac1 against pathological tau protein; here, we present the results of a further 72 weeks of follow-up on those patients. METHODS: We did a phase 1, 72-week, open-label study of AADvac1 in patients with mild to moderate Alzheimer's disease who had completed the preceding phase 1 study. Patients who were previously treated with six doses of AADvac1 at monthly intervals received two booster doses at 24-week intervals. Patients who were previously treated with only three doses received another three doses at monthly intervals, and subsequently two boosters at 24-week intervals. The primary objective was the assessment of long-term safety of AADvac1 treatment. Secondary objectives included assessment of antibody titres, antibody isotype profile, capacity of the antibodies to bind to AD tau and AADvac1, development of titres of AADvac1-induced antibodies over time, and effect of booster doses; cognitive assessment via 11-item Alzheimer's Disease Assessment Scale cognitive assessment (ADAS-Cog), Category Fluency Test and Controlled Oral Word Association Test; assessment of brain atrophy via magnetic resonance imaging (MRI) volumetry; and assessment of lymphocyte populations via flow cytometry. RESULTS: The study was conducted between 18 March 2014 and 10 August 2016. Twenty-six patients who completed the previous study were enrolled. Five patients withdrew because of adverse events. One patient was withdrawn owing to noncompliance. The most common adverse events were injection site reactions (reported in 13 [50%] of vaccinated patients). No cases of meningoencephalitis or vasogenic oedema were observed. New micro-haemorrhages were observed only in one ApoE4 homozygote. All responders retained an immunoglobulin G (IgG) antibody response against the tau peptide component of AADvac1 over 6 months without administration, with titres regressing to a median 15.8% of titres attained after the initial six-dose vaccination regimen. Booster doses restored previous IgG levels. Hippocampal atrophy rate was lower in patients with high IgG levels; a similar relationship was observed in cognitive assessment. CONCLUSIONS: AADvac1 displayed a benign safety profile. The evolution of IgG titres over vaccination-free periods warrants a more frequent booster dose regimen. The tendency towards slower atrophy in MRI evaluation and less of a decline in cognitive assessment in patients with high titres is encouraging. Further trials are required to expand the safety database and to establish proof of clinical efficacy of AADvac1. TRIAL REGISTRATION: The studies are registered with the EU Clinical Trials Register and ClinicalTrials.gov : the preceding first-in-human study under EudraCT 2012-003916-29 and NCT01850238 (registered on 9 May 2013) and the follow-up study under EudraCT 2013-004499-36 and NCT02031198 (registered 9 Jan 2014), respectively.

Vaccine Therapy, Oncolytic Viruses, and Gliomas.

After years of active research and refinement, vaccine therapy and oncolytic viruses are becoming part of the arsenal in the treatment of gliomas. In contrast to standard treatment with radiation therapy and chemotherapy, vaccines are more specific to the patient and the tumor. The majority of ongoing vaccine trials are investigating peptide, heat shock protein, and dendritic cell vaccines. The immunosuppression triggered by the tumor itself and by its treatment is a major obstacle to vaccine and oncolytic virus therapy. Thus, combination therapy with different agents that affect the immune system will probably be necessary.

Vaccine-induced Aß-specific CD8+ T cells do not trigger autoimmune neuroinflammation in a murine model of Alzheimer's disease.

BACKGROUND: Active immunization against Aß was reported to have a therapeutic effect in murine models of Alzheimer's disease. Clinical Aß vaccination trial AN1792 was interrupted due to the development in 6 % of the patients of meningoencephalitis likely involving pro-inflammatory CD4(+) T cells. However, the potential implication of auto-aggressive anti-Aß CD8(+) T cells has been poorly investigated. METHODS: Potential MHC-I-restricted Aß-derived epitopes were first analyzed for their capacity to recruit functional CD8(+) T cell responses in mouse models. Their impact on migration of CD8(+) T cells into the brain parenchyma and potential induction of meningoencephalitis and/or neuronal damage was investigated upon vaccination in the APPPS1 mouse model of AD. RESULTS: We identified one nonamer peptide, Aß33-41, which was naturally processed and presented in association with H-2-D(b) molecule on neurons and CD11b(+) microglia. Upon optimization of anchor residues for enhanced binding to H-2-D(b), immunization with the modified Aß33-41NP peptide elicited Aß-specific IFNγ-secreting CD8(+) T cells, which are cytotoxic towards Aß-expressing targets. Whereas T cell infiltration in the brain of APPPS1 mice is dominated by CD3(+)CD8(-) T cells and increases with disease evolution between 4 and 7 months of age, a predominance of CD3(+)CD8(+) over CD3(+)CD8(-) cells was observed in 6- to 7-month-old APPPS1 but not in WT animals, only after vaccination with Aß33-41NP. The number of CD11b(+) mononuclear phagocytes, which significantly increases with age in the brain of APPPS1 mice, was reduced following immunization with Aß33-41NP. Despite peripheral activation of Aß-specific CD8(+) cytotoxic effectors and enhanced infiltration of CD8(+) T cells in the brain of Aß33-41NP-immunized APPPS1 mice, no clinical signs of severe autoimmune neuroinflammation were observed. CONCLUSIONS: Altogether, these results suggest that Aß-specific CD8(+) T cells are not major contributors to meningoencephalitis in response to Aß vaccination.

First clinical results of a personalized immunotherapeutic vaccine against recurrent, incompletely resected, treatment-resistant glioblastoma multiforme (GBM) tumors, based on combined allo- and auto-immune tumor reactivity.

Glioblastoma multiforme (GBM) patients have a poor prognosis. After tumor recurrence statistics suggest an imminent death within 1-4.5 months. Supportive preclinical data, from a rat model, provided the rational for a prototype clinical vaccine preparation, named Gliovac (or ERC 1671) composed of autologous antigens, derived from the patient's surgically removed tumor tissue, which is administered together with allogeneic antigens from glioma tissue resected from other GBM patients. We now report the first results of the Gliovac treatment for treatment-resistant GBM patients. Nine (9) recurrent GBM patients, after standard of care treatment, including surgery radio- and chemotherapy temozolomide, and for US patients, also bevacizumab (Avastin™), were treated under a compassionate use/hospital exemption protocol. Gliovac was given intradermally, together with human GM-CSF (Leukine(®)), and preceded by a regimen of regulatory T cell-depleting, low-dose cyclophosphamide. Gliovac administration in patients that have failed standard of care therapies showed minimal toxicity and enhanced overall survival (OS). Six-month (26 weeks) survival for the nine Gliovac patients was 100% versus 33% in control group. At week 40, the published overall survival was 10% if recurrent, reoperated patients were not treated. In the Gliovac treated group, the survival at 40 weeks was 77%. Our data suggest that Gliovac has low toxicity and a promising efficacy. A phase II trial has recently been initiated in recurrent, bevacizumab naïve GBM patients (NCT01903330).

A patient with an allergy emergency.

Anaphylaxis is a severe life-threatening systemic reaction that otolaryngologists may come in contact with through emergency cases, or in their offices when delivering allergy immunotherapy. Rapid recognition of the entity should be followed by epinephrine administration. Anaphylaxis causes, including a hypothetical scenario, are described. Various risk factors for anaphylaxis, such as ß-blocker use, are discussed. The differential diagnosis of anaphylaxis and adjunct treatment are explained.

Safety and effectiveness of autoinoculation therapy in cutaneous warts: a double--blind, randomized, placebo--controlled study.

BACKGROUND: In spite of the availability of multiple treatment options, viral warts are known for their persistence and recurrence, causing frustration to patients and treating physicians. AIMS: To study the effectiveness and safety of autoinoculation as a treatment modality in cutaneous warts. METHODS: A double-blind, placebo-controlled study was carried out. In the treatment group, full-thickness warty tissue was excised, minced and implanted in a small dermal pocket. In the control group, warty tissue was only excised and not implanted, though a dermal pocket was made. Patients were evaluated every four weeks with lesion counts. The procedure was repeated at 4 and 8 weeks. Response was assessed at each visit and at 12 weeks. RESULTS: Forty-eight patients with cutaneous warts (male: female=32:16) were randomized into autoinoculation and control groups. The number of warts at baseline was comparable in both groups (P=0.293). Reduction in the number of warts was significantly more in the autoinoculation group (8.50±13.88) than in the control group (10.04±5.80) from 8 weeks onwards (P=0.010). Complete resolution occurred only in the autoinoculation group, in 62.5% of cases. Adverse effects were seen in 11 patients, including infection of the donor site (5 cases), keloid formation (3) and hypopigmentation (3). CONCLUSION: Autoinoculation may be an effective therapeutic modality for cutaneous warts and two sessions may be required for optimum results.

Antigen-specific active immunotherapy for ovarian cancer.

BACKGROUND: Despite advances in chemotherapy, prognosis of ovarian cancer remains poor. Antigen-specific active immunotherapy aims to induce tumour-antigen-specific anti-tumour immune responses as an alternative treatment for ovarian cancer. OBJECTIVES: To assess the feasibility of antigen-specific active immunotherapy for ovarian cancer. Primary outcomes are clinical efficacy and antigen-specific immunogenicity with carrier-specific immunogenicity and side effects as secondary outcomes. SEARCH METHODS: For the previous version of this review, a systematic search of the Cochrane Central Register of Controlled Trials (CENTRAL) 2009, Issue 3, Cochrane Gynaecological Cancer Group Specialized Register, MEDLINE and EMBASE databases and clinicaltrials.gov was performed (1966 to July 2009). We conducted handsearches of the proceedings of relevant annual meetings (1996 to July 2009).For this update of the review the searches were extended to October 2013. SELECTION CRITERIA: Randomised controlled trials (RCTs), as well as non-randomised non-controlled studies that included participants with epithelial ovarian cancer, irrespective of stage of disease, and treated with antigen-specific active immunotherapy, irrespective of type of vaccine, antigen used, adjuvant used, route of vaccination, schedule, and reported clinical or immunological outcomes. DATA COLLECTION AND ANALYSIS: Two reviews authors independently performed the data extraction. Risk of bias was evaluated for RCTs according to standard methodological procedures expected by The Cochrane Collabororation or for non-RCTs using a selection of quality domains deemed best applicable to the non-randomised non-controlled studies. MAIN RESULTS: Fifty-five studies were included (representing 3051 women with epithelial ovarian cancer). Response definitions showed substantial variation between trials, which makes comparison of trial results unreliable. Information on adverse events was frequently limited. Furthermore, reports of both RCTs and non-RCTs frequently lacked the relevant information necessary to assess risk of bias. Serious biases in most of the included trials can therefore not be ruled out.The largest body of evidence is currently available for CA-125 targeted antibody therapy (16 studies: 2339 participants). Non-RCTs of CA-125 targeted antibody therapy suggests increased survival in humoral and/or cellular responders. However, four large randomised placebo-controlled trials did not show any clinical benefit despite induction of immune responses in approximately 60% of participants.Other small studies targeting many different tumour antigens showed promising immunological results. As these strategies have not yet been tested in RCTs, no reliable inferences about clinical efficacy can be made. Given the promising immunological results, limited side effects and toxicity exploration of clinical efficacy in large well-designed RCTs may be worthwhile. AUTHORS' CONCLUSIONS: We conclude that despite promising immunological responses, no clinically effective antigen-specific active immunotherapy is yet available for ovarian cancer. Results should be interpreted cautiously as there was a significant lack of relevant information for the assessment of risk of bias in both RCTs and non-RCTs.

Inflammatory adverse events are associated with disease-free survival after vaccine therapy among patients with melanoma.

BACKGROUND: Multipeptide vaccines for melanoma may cause inflammatory adverse events (IAE). We hypothesize that IAE are associated with a higher rate of immune response (IR) to vaccination and improved clinical outcomes. METHODS: Adult patients with resected, high-risk (stage IIB to IV) melanoma were vaccinated with a combination of 12 class I major histocompatibility complex (MHC)-restricted melanoma epitopes, and IAE were recorded. A separate category for hypopigmentation (vitiligo) was also assessed. CD8(+) T cell IR was assessed by direct interferon gamma ELISpot analysis. Overall survival and disease-free survival were analyzed by Cox proportional hazard modeling. RESULTS: Out of 332 patients, 57 developed IAE, the majority of which were dermatologic (minimum Common Terminology Criteria for Adverse Events [CTCAE] grade 3). Most nondermatologic IAE were CTCAE grade 1 and 2. Vitiligo developed in 23 patients (7 %). A total of 174 patients (53 %) developed a CD8(+) response. Presence of IAE was significantly associated with development of IR (70 vs. 49 %, p = 0.005) and with disease-free survival (hazard ratio 0.54, p = 0.043). There were no significant associations relating vitiligo or IR alone with clinical outcomes. CONCLUSIONS: IAE are associated with a higher rate of CD8(+) T cell response after vaccination therapy for high-risk melanoma. Our findings suggest either that antitumor activity induced by class I MHC-restricted peptide vaccines may depend on immunologic effects beyond simple expansion of CD8(+) T cells or that the intrinsic inflammatory response of patients contributes to clinical outcome in melanoma.

Clinical trials of amyloid-based immunotherapy for Alzheimer's disease: end of beginning or beginning of end?

INTRODUCTION: Amyloid deposit and hyperphosphorylated Tau protein contribute to pathological changes seen in Alzheimer's disease (AD) and imply that removal may reverse the cognitive decline. Immunotherapy is a potential way of reducing the load of amyloid or Tau in the brain. AREAS COVERED: This review summarizes recent clinical trials that have investigated immunotherapy to treat AD and its potential mechanisms. In addition, the potential opportunities as well as challenges of immunotherapy for AD in clinical trials are also discussed. EXPERT OPINION: Amyloid-based immunotherapy for AD is a novel method with potential; however, some clinical trials were terminated because of the adverse effects. Further studies need to determine the following questions: (i) which is better, passive, or active immunotherapy; (ii) which could be used for the vaccine, amyloid or Tau; (iii) which is better, short- or long-antigen vaccine; and (iv) the route of delivery for antigen or antibody.

Phase II study of personalized peptide vaccination for refractory bone and soft tissue sarcoma patients.

Refractory bone and soft tissue sarcomas are challenging diseases to treat because of their robustness to chemotherapy. Although cancer vaccines have the potential to become an attractive treatment modality, their progress has been hampered by the presence of many subtypes of sarcomas and different human leukocyte antigen (HLA)-types. We investigated whether personalized peptide vaccination (PPV) would be feasible for the vast majority of sarcoma patients. Twenty refractory bone and soft tissue sarcoma patients with nine different subtypes and 11 different HLA-class IA phenotypes were enrolled in this study. A maximum of four HLA-matched peptides showing higher peptide-specific IgG responses in pre-vaccination plasma were selected from 31 pooled peptide candidates applicable for the HLA-A2, -A3, -A11, -A24, -A26, -A31, and -A33 types, and were subcutaneously administered weekly for 6 weeks and bi-weekly thereafter. Measurement of peptide-specific CTL and IgG responses along with other laboratory analyses were conducted before and after vaccination. No patients were excluded by either sarcoma subtypes or different HLA-types. No severe adverse events associated with PPV were observed in any patients. Peptide-specific immunological boosting was observed in the post-vaccination samples from the majority of patients. Tumor reduction of the lung metastasis and a long stable disease was observed in each case, and the median overall survival time of the 20 cases was 9.6 months. Taken together, PPV could be feasible for the vast majority of refractory sarcoma patients because of the safety and higher rates of immunological responses regardless of the presence of different sarcoma subtypes and various HLA-types.

Addition of algenpantucel-L immunotherapy to standard adjuvant therapy for pancreatic cancer: a phase 2 study.

BACKGROUND: Despite continued investigation, limited progress has been made in the adjuvant treatment of resected pancreatic cancer. Novel or targeted therapies are needed. METHODS: Multi-institutional, open-label, dose-finding, phase 2 trial evaluating the use of algenpantucel-L (NewLink Genetics Corporation, Ames, IA) immunotherapy in addition to chemotherapy and chemoradiotherapy in the adjuvant setting for resected pancreatic cancer (ClinicalTrials.gov identifier, NCT00569387). The primary outcome was 12-month disease-free survival. Secondary outcomes included overall survival and toxicity. RESULTS: Seventy patients were treated with gemcitabine and 5-fluorouracil-based chemoradiotherapy as well as algenpantucel-L (mean 12 doses, range 1-14). After a median follow-up of 21 months, the 12-month disease-free survival was 62 %, and the 12-month overall survival was 86 %. The most common adverse events were injection site pain and induration. CONCLUSIONS: The addition of algenpantucel-L to standard adjuvant therapy for resected pancreatic cancer may improve survival. A multi-institutional, phase 3 study is ongoing (ClinicalTrials.gov identifier, NCT01072981).

Exploratory clinical studies of a synthetic HIV-1 Tat epitope vaccine in asymptomatic treatment-naïve and antiretroviral-controlled HIV-1 infected subjects plus healthy uninfected subjects.

TUTI-16 is a synthetic universal HIV-1 Tat epitope vaccine, designed to induce anti-Tat antibodies that block the function of circulating Tat, an HIV encoded protein secreted by HIV-1 infected cells. Circulating Tat activates CD4 T cells, permitting HIV replication and sustained viremia. Safety, immunogenicity and antiretroviral potential of TUTI-16 were explored in a randomized double-blind dose-escalating study in asymptomatic treatment-naïve HIV-1 infected subjects. TUTI-16 was safe, with mild local and systemic injection-related adverse reactions, but the antibody response was barely detectable. Surprisingly, a highly statistically significant reduction of HIV-1 viral load was found in the lowest 30 µg vaccine dose group (p < 0.01) but not at the higher doses. We posited that an anti-Tat antibody response below the limit of detection inhibited HIV viral load at this dose, an effect nullified at higher vaccine doses by activating cytokines induced by adjuvant components in TUTI-16. To clarify this immunogenicity/activation conundrum open label immunogenicity studies were performed in healthy HIV uninfected and aviremic ART-controlled HIV-infected subjects. These established that (1) healthy HIV negative subjects had robust antibody responses, maximal with 1 mg TUTI-16, (2) ART-controlled aviremic HIV infected subjects had similarly robust antibody responses, and (3) adjuvant-induced increases of HIV viral load did not occur in the presence of ART. These studies provided us a basis for the design of a protocol to explore the therapeutic potential of TUTI-16 vaccination to provide drug free control of HIV-1 viremia.

Active specific immunotherapy targeting the Wilms' tumor protein 1 (WT1) for patients with hematological malignancies and solid tumors: lessons from early clinical trials.

There is a growing body of evidence that Wilms' tumor protein 1 (WT1) is a promising tumor antigen for the development of a novel class of universal cancer vaccines. Recently, in a National Cancer Institute prioritization project, WT1 was ranked first in a list of 75 cancer antigens. In this light, we exhaustively reviewed all published cancer vaccine trials reporting on WT1-targeted active specific immunotherapy in patients with hematological malignancies and solid tumors. In all clinical trials, vaccine-induced immunological responses could be detected. Importantly, objective clinical responses (including stable disease) were observed in 46% and 64% of evaluable vaccinated patients with solid tumors and hematological malignancies, respectively. Immunogenicity of WT1-based cancer vaccines was demonstrated by the detection of a specific immunological response in 35% and 68% of evaluable patients with solid tumors and hematological malignancies, respectively. In order to become part of the armamentarium of the modern oncologist, it will be important to design WT1-based immunotherapies applicable to a large patient population, to standardize vaccination protocols enabling systematic review, and to further optimize the immunostimulatory capacity of the vaccine components. Moreover, improved immunomonitoring tools that reveal clinically relevant T-cell responses will further shape the ideal WT1 immunotherapy strategy. In conclusion, the clinical results obtained so far in WT1-targeted cancer vaccine trials reveal an untapped potential for inducing cancer immunity with minimal side effects and hold promise for a new adjuvant treatment against residual disease and against cancer relapse.