Vaccine therapy in hematologic malignancies

Avigan, David; Rosenblatt, Jacalyn

doi:10.1182/blood-2017-11-785873

Cited by 43 publications

(37 citation statements)

References 82 publications

(100 reference statements)

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“…One innovative strategy to boost the GVL effect without GVHD is to target leukemia‐associated antigens such as PR1, WT1, and BCR/ABL . Cytotoxic T cells immune responses specific to these proteins could be augmented with vaccination.…”

Section: Cellular Therapiesmentioning

confidence: 99%

Prevention of relapse after allogeneic stem cell transplantation in acute myeloid leukemia: Updates and challenges

2019

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Acute myeloid leukemia (AML) is a disease with heterogeneous prognosis based on the clinical, cytogenetic, and molecular profile of the patient. Despite high post-induction remission rates in adult patients up to 40% of patients relapse. Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is an effective and potentially curative post-remission treatment for AML. 1 The antileukemic effect of allo-HSCT depends on the cytotoxicity of the pretransplant conditioning therapy and the posttransplant graft versus leukemia (GVL) effect. In a meta-analysis, allo-HSCT significantly improves survival in patients in first complete remission (CR) with poor-risk and intermediate-risk cytogenetic abnormalities (poor-risk: HR -0.73; 95% CI, 0.59-0.90); (intermediate-risk AML: HR, 0.83%-95% CI, 0.74-0.93). 2,3 The introduction of non-myeloablative (NMA) and reduced intensity conditioning (RIC) regimens, advances in HLA-matching, improved supportive care, and tailored graft versus host disease (GVHD) prophylaxis have allowed for a larger application of allo-HSCT to older patients and those with comorbidities. Although Abstract Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is a potentially curative treatment for acute myeloid leukemia (AML). Reduced intensity regimens, alternative graft sources, advances in HLA-matching, improved supportive care, and tailored graft versus host disease (GVHD) prophylaxis have led to a wider application of allo-HSCT to eligible patients. Unfortunately, 30-40% of patients with AML will relapse after transplant and this is the major cause of treatment failure. Careful consideration should be paid in choosing the type of graft, graft source, and conditioning regimen to minimize the risk of disease recurrence. In addition, maintenance therapy following allo-HSCT is a potential method to keep the disease in remission, especially in those with high-risk disease characteristics. Pharmacological targeted agents with low side effect profile such as tyrosine kinase inhibitors, hypomethylating agents (HMAs), HDAC inhibitors, antibody drug conjugates (ADCs), isocitrate dehydrogenase inhibitors, and hedgehog inhibitors may prevent relapse in posttransplant setting and are under investigation. Immunological therapies including donor lymphocyte infusions (DLIs), natural killer (NK) cell therapy, peptide vaccine targeting tumor antigens, and adoptive T-cell therapies all hold promises in this area as well. As targeted agents and immunotherapies continue to be developed, patients at high risk of recurrence may benefit from prophylactic maintenance therapy. Here we review the current landscape in this rapidly evolving clinical setting. K E Y W O R D S Acute myeloid leukemia, Allogeneic Transplant, Immunotherapy, Posttransplant relapse, Targeted agents

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Section: Cellular Therapiesmentioning

confidence: 99%

Prevention of relapse after allogeneic stem cell transplantation in acute myeloid leukemia: Updates and challenges

2019

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“…AML-dendritic cell fusion vaccines have the benefit of overcoming defective antigen presenting functions of leukemic cells and of not requiring a priori selection of antigens. Moreover, by presenting multiple antigens with the potential to engage multiple TCRs, a diverse T cell response could be elicited (39, 40).…”

Section: Features Of Immune Dysregulation In Amlmentioning

confidence: 99%

The Interplay Between the Genetic and Immune Landscapes of AML: Mechanisms and Implications for Risk Stratification and Therapy

2019

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AML holds a unique place in the history of immunotherapy by virtue of being among the first malignancies in which durable remissions were achieved with “adoptive immunotherapy,” now known as allogeneic stem cell transplantation. The successful deployment of unselected adoptive cell therapy established AML as a disease responsive to immunomodulation. Classification systems for AML have been refined and expanded over the years in an effort to capture the variability of this heterogeneous disease and risk-stratify patients. Current systems increasingly incorporate information about cytogenetic alterations and genetic mutations. The advent of next generation sequencing technology has enabled the comprehensive identification of recurrent genetic mutations, many with predictive power. Recurrent genetic mutations found in AML have been intensely studied from a cell intrinsic perspective leading to the genesis of multiple, recently approved targeted therapies including IDH1/2-mutant inhibitors and FLT3-ITD/-TKD inhibitors. However, there is a paucity of data on the effects of these targeted agents on the leukemia microenvironment, including the immune system. Recently, the phenomenal success of checkpoint inhibitors and CAR-T cells has re-ignited interest in understanding the mechanisms leading to immune dysregulation and suppression in leukemia, with the objective of harnessing the power of the immune system via novel immunotherapeutics. A paradigm has emerged that places crosstalk with the immune system at the crux of any effective therapy. Ongoing research will reveal how AML genetics inform the composition of the immune microenvironment paving the way for personalized immunotherapy.

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“…However, it is unclear when and how the vaccine should be used to produce optimal treatment efficacy (77). Another vaccination strategy is the use of gene-transduced tumor cell vaccine (GAVX) where cells are modified to express GM-CSF to recruit DCs to the site of intradermal vaccination to elicit an anti-tumour immune response (78). A phase II trial (NCT01773395) is being conducted to evaluate the efficacy of GVAX following allogeneic HSCT.…”

Section: Application Of Immunotherapeutic Concepts For the Treatment mentioning

confidence: 99%

Recent Treatment Advances and the Role of Nanotechnology, Combination Products, and Immunotherapy in Changing the Therapeutic Landscape of Acute Myeloid Leukemia

Chen

Gilabert-Oriol²,

Bally

et al. 2019

Pharm Res

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Acute myeloid leukemia (AML) is the most common acute leukemia that is becoming more prevalent particularly in the older (65 years of age or older) population. For decades, “7 + 3” remission induction therapy with cytarabine and an anthracycline, followed by consolidation therapy, has been the standard of care treatment for AML. This stagnancy in AML treatment has resulted in less than ideal treatment outcomes for AML patients, especially for elderly patients and those with unfavourable profiles. Over the past two years, six new therapeutic agents have received regulatory approval, suggesting that a number of obstacles to treating AML have been addressed and the treatment landscape for AML is finally changing. This review outlines the challenges and obstacles in treating AML and highlights the advances in AML treatment made in recent years, including Vyxeos®, midostaurin, gemtuzumab ozogamicin, and venetoclax, with particular emphasis on combination treatment strategies. We also discuss the potential utility of new combination products such as one that we call “EnFlaM”, which comprises an encapsulated nanoformulation of flavopiridol and mitoxantrone. Finally, we provide a review on the immunotherapeutic landscape of AML, discussing yet another angle through which novel treatments can be designed to further improve treatment outcomes for AML patients.

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Vaccine therapy in hematologic malignancies

Cited by 43 publications

References 82 publications

Prevention of relapse after allogeneic stem cell transplantation in acute myeloid leukemia: Updates and challenges

Prevention of relapse after allogeneic stem cell transplantation in acute myeloid leukemia: Updates and challenges

The Interplay Between the Genetic and Immune Landscapes of AML: Mechanisms and Implications for Risk Stratification and Therapy

Recent Treatment Advances and the Role of Nanotechnology, Combination Products, and Immunotherapy in Changing the Therapeutic Landscape of Acute Myeloid Leukemia

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