An autologous leukemia cell vaccine prevents murine acute leukemia relapse after cytarabine treatment

Gibbins, John D.; Ancelet, Lindsay R.; Weinkove, Robert; Compton, Benjamin J.; Painter, Gavin F.; Petersen, Troels R.; Hermans, Ian F.

doi:10.1182/blood-2014-04-568956

Cited by 25 publications

(30 citation statements)

References 73 publications

(75 reference statements)

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“…We have recently shown that irradiated autologous leukemia cells pulsed with the glycolipid invariant natural killer T (iNKT) cell agonist a-galactosylceramide (a-GalCer) can act as a simple and effective vaccine for acute leukemia. 4 We found that while the vaccine elicited potent anti-leukemic responses, dependent on the cross-presenting Langerin C subset of dendritic cells and both CD4 C and CD8 C T effector responses, efficacy in mice with established disease was hindered by leukemia-induced immune suppression. This suppression was attributed to an increase in the proportion of T regulatory cells, myeloid derived suppressor cells and direct suppression on effector cells by the leukemia itself, with CD4 C T cell responses more severely affected than CD8 C T cell responses.…”

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confidence: 85%

“…7 Although acute leukemia induction chemotherapy can suppress the immune system, 8 recent cytarabine chemotherapy did not prevent effective vaccination in our model. 4 Effective vaccination in patients will require both an intact iNKT cell axis and a T cell repertoire with tumor specificity. We have previously shown that iNKT cells from patients treated with chemotherapy for an indolent leukemia retained their in vitro ability to proliferate in response to a-GalCer treated autologous leukemia cells.…”

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confidence: 99%

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An adjuvanted whole cell vaccine as post-remission immunotherapy for acute leukemia

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confidence: 85%

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confidence: 99%

An adjuvanted whole cell vaccine as post-remission immunotherapy for acute leukemia

et al. 2015

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“…Similar strategies have been translated to the targeting of leukemia. An α-GalCer adjuvant vaccine with irradiated acute leukemia cells was tested in mice as a possibility for targeting leukemia 165 . Unfortunately, the vaccine proved to only be effective at preventing onset and relapse rather than mitigating an already established leukemia 165 .…”

Section: Targeting the Immune Cell Populations Using Vaccines And mentioning

confidence: 99%

“…An α-GalCer adjuvant vaccine with irradiated acute leukemia cells was tested in mice as a possibility for targeting leukemia 165 . Unfortunately, the vaccine proved to only be effective at preventing onset and relapse rather than mitigating an already established leukemia 165 . Other approaches utilized a multi-epitope vaccine for CML by delivering the fusion protein BCR-ABL and Wilms’ tumor 1 (WT1) epitopes 166 .…”

Section: Targeting the Immune Cell Populations Using Vaccines And mentioning

confidence: 99%

Drug discovery and therapeutic delivery for the treatment of B and T cell tumors

Stephenson

Singh

2017

Advanced Drug Delivery Reviews

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Hematological malignancies manifest as lymphoma, leukemia, and myeloma, and remain a burden on society. From initial therapy to endless relapse-related treatment, societal burden is felt not only in the context of healthcare cost, but also in the compromised quality of life of patients. Long-term therapeutic strategies have become the standard in keeping hematological malignancies at bay as these cancers develop resistance to each round of therapy with time. As a result, there is a continual need for the development of new drugs to combat resistant disease in order to prolong patient life, if not to produce a cure. This review aims to summarize advances in targeting lymphoma, leukemia, and myeloma in both cutting-edge and well established platforms. Current standard of treatment will be reviewed for these malignancies and emphasis will be made on new therapy development in the areas of antibody engineering, epigenetic small molecule inhibiting drugs, vaccine development, and chimeric antigen receptor cell engineering. In addition, platforms for the delivery of these and other drugs will be reviewed including antibody-drug conjugates, micro- and nanoparticles, and multimodal hydrogels. Lastly, we propose that tissue engineered constructs for hematological malignancies are the missing link in targeted drug discovery alongside mouse and patient-derived xenograft models.

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“…For successful use of tumor cell vaccines, the usage of appropriate adjuvant is essential. Recently, Gibbins et al reported that an intravenously administered vaccine consisting of irradiated leukemia cells loaded with the natural killer T (NKT)-cell agonist alpha-galactosylceramide (alpha-GalCer) was effective in a mouse leukemia model (8).…”

Section: Vaccines For Hematological Malignanciesmentioning

confidence: 99%

Wilms tumor 1 peptide vaccination after hematopoietic stem cell transplant in leukemia patients

Hosen

Maeda

Hashii

et al. 2016

Stem Cell Investig.

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Although the prognosis of leukemia patients after allogeneic hematopoietic stem cell transplantation (HSCT) has greatly improved, relapse is still a major cause of death after HSCT. Cancer vaccines may have the potential to enhance the graft-versus-leukemia (GVL) effect. The post-allogeneic HSCT period provides a unique platform for vaccination, because (I) tumor burden is minimal, (II) lymphopenia allows for rapid expansion of cytotoxic T cells (CTLs), (III) donor-derived CTLs are not exhausted, (IV) inflammation is caused by alloreactions, and (V) the abundance of regulatory T cells is low due to their late recovery. Tumor cell lysates, dendritic cells (DCs), and peptides derived from leukemiaassociated antigens (LAAs) have been used as vaccines. Clinical trials with several types of vaccines for post-HSCT patients revealed that the vaccination induced an immunological response and might benefit patients with minimal residual disease; however, the efficacy of this approach must be examined in randomized studies. In addition, it is important to consider the combination of cancer vaccine with checkpoint antibodies, recently shown to be useful in treating leukemia relapse after HSCT. Vaccines for hematological malignanciesIn several types of cancers, allogeneic tumor cells expressing granulocyte-macrophage colony-stimulating factor (GM-CSF) (GVAX) were tested as vaccine (3)(4)(5). For example, K562 cells expressing GM-CSF were used as vaccine for CML patients. In some patients, the abundance of CML cells decreased after immunotherapy, and this effect was associated with the induction of high-titer IgG antibodies against multiple leukemia-associated antigens (LAAs) (6). In another trial by Borrello et al., pre-auto HSCT patients were immunized with autologous leukemia cells mixed with GM-CSF-secreting K562 cells (7). A decrease in Wilms tumor 1 (WT1) transcripts in blood was noted in 69% of patients after immunotherapy, and was associated with longer 3-year relapse-free survival (61% in the immunized group vs. 0% in the nonimmunized group). For successful use of tumor cell vaccines, the usage of appropriate adjuvant is essential. Recently, Gibbins et al. reported that an intravenously administered vaccine consisting of irradiated leukemia cells loaded with the natural killer T (NKT)-cell agonist alpha-galactosylceramide (alpha-GalCer) was effective in a mouse leukemia model (8).Dendritic cell (DC)-based vaccines represent another effective strategy. For example, leukemic DCs generated from peripheral blood of CML patients were used as a vaccine and shown to elicit a tumor-reactive T cells response (9). DC fusions with leukemia cells or DCs loaded with tumor cell lysates also induced a potent tumor immune response (10). In addition, vaccination with WT1 mRNAelectroporated DCs induces molecular remission in AML patients (11).Several kinds of peptide vaccines have been developed. For example, LAA-derived peptides (12) and DNA (13) have been used as vaccines in combination with adjuvants. BCR-ABL for Phil...

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An autologous leukemia cell vaccine prevents murine acute leukemia relapse after cytarabine treatment

Abstract: Key Points A cellular vaccine incorporating the glycolipid α-galactosylceramide prevents relapse of acute leukemia following cytarabine chemotherapy.

Cited by 25 publications

References 73 publications

An adjuvanted whole cell vaccine as post-remission immunotherapy for acute leukemia

An adjuvanted whole cell vaccine as post-remission immunotherapy for acute leukemia

Drug discovery and therapeutic delivery for the treatment of B and T cell tumors

Wilms tumor 1 peptide vaccination after hematopoietic stem cell transplant in leukemia patients

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