Immunotherapy in hematologic malignancies: past, present, and future

Im, Annie; Pavletić, Steven Z.

doi:10.1186/s13045-017-0453-8

Cited by 91 publications

(71 citation statements)

References 86 publications

(71 reference statements)

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“…We aimed to understand the influence of Mϕ and NK cells on CML survival, particularly on how Mϕ modulates NK cytotoxicity. We focused on CML because of the lack of studies on Mϕ–NK interactions in hematological tumors, and that solid tumors are well known to be resistant to immunotherapeutic efforts, whereas hematological malignancies are responsive owing to the accessibility of immune cells to the leukemic cells . Moreover, we found an increase in the ratio of innate to adaptive immune cells in CML bone marrow compared with nonleukemia controls, further prompting us to focus our investigation of Mϕ and NK cells on CML.…”

Section: Discussionmentioning

confidence: 99%

Macrophages protect mycoplasma‐infected chronic myeloid leukemia cells from natural killer cell killing

et al. 2020

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Macrophages (M/) have been reported to downmodulate the cytotoxicity of natural killer (NK) cell against solid tumor cells. However, the collaborative role between NK cells and M/ remains underappreciated, especially in hematological cancers, such as chronic myeloid leukemia (CML). We observed a higher ratio of innate immune cells (M/ and NK) to adaptive immune cells (T and B cells) in CML bone marrow aspirates, prompting us to investigate the roles of NK and M/ in CML. Using coculture models simulating the tumor inflammatory environment, we observed that M/ protects CML from NK attack only when CML was itself mycoplasmainfected and under chronic infection-inflammation condition. We found that the M/-protective effect on CML was associated with the maintenance of CD16 level on the NK cell membrane. Although the NK membrane CD16 (mCD16) was actively shed in M/ + NK + CML trioculture, the NK mCD16 level was maintained, and this was independent of the modulation of sheddase by tissue inhibitor of metalloproteinase 1 or inhibitory cytokine transforming growth factor beta. Instead, we found that this process of NK mCD16 maintenance was conferred by M/ in a contact-dependent manner. We propose a new perspective on anti-CML strategy through abrogating M/mediated retention of NK surface CD16.

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Section: Discussionmentioning

confidence: 99%

Macrophages protect mycoplasma‐infected chronic myeloid leukemia cells from natural killer cell killing

et al. 2020

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“…The main targets are cluster designation (CD) proteins that are usually highly expressed on malignant cells in specific NHLs. The chimeric anti‐CD20 MA (Rituximab) was the first and the most clinically used and studied among the target drugs . Afterwards several other MA unconjugates, or radioconjugates (iodine‐131 anti‐D20, yttrium‐90 anti‐CD20), have been produced.…”

Section: Therapies For Nhl and Targets Detectable By Ln‐fnacmentioning

confidence: 99%

“…The main targets of MAs are cluster designation (CD) proteins, each of them addressed against specific antigens with one or more specific entities as clinical target; namely: blinatumomab (anti‐CD19) in B‐cell precursor anaplastic large cell lymphoma, obinutuzumab (anti‐CD20) in FL and CLL, ofatumumab (anti‐CD20) in CLL, rituximab (anti‐CD20) in CD20 positive FL, CLL and DLBCL, epratuxumab (anti‐CD22), inotuzumab (anti‐CD22) in B‐cell precursor anaplastic large cell lymphoma, moxetumomab (anti‐CD22) in HCL, brentuximab (anti‐CD30) in cHL, ALCL, CD30+ MF and systemic ALCL, daratumumab (anti‐CD38) in multiple myeloma (MM), alemtuzumab (anti‐CD52) in CLL and T‐cell NHL. Other monoclonal antibodies are addressed against different antigens such as apolizumab (antiHLA‐DR), alentuzumab (Campat‐1H) and anti‐CD40 . Table provides a list of the most used monoclonal antibodies, either in untreated or previously treated patients, with molecular target(s), clinical indications and Food and Drug Administration approvals.…”

Section: Therapies For Nhl and Targets Detectable By Ln‐fnacmentioning

confidence: 99%

Lymph node fine‐needle cytology in the era of personalised medicine. Is there a role?

et al. 2019

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The 2016 World Health Organisation revised classification of lymphoma has sub‐classified well‐defined entities and added a number of provisional entities on the basis of new knowledge on genetic, epigenetics and phenotypical data; prognostic and predictive features are also part of this classification. New knowledge on well‐defined entities further enlightens the mechanisms of lymphomagenesis, which are more complex and multifactorial than once believed. Therapies are also more complex because traditional clinical trials have been integrated with new drugs and compounds with unique mechanisms of actions against distinct molecular targets. As lymphoma acquires additional genetic and phenotypic features over the time, pathological assessment is also necessary. Histological evaluation and tissue collection by surgical biopsies are necessary for phenotypical and molecular purposes; however, these are demanding procedures for both the patient and the health care system. At the same time, the choice of the best treatment for a specific entity, in different phases and different patients requires information that may not be available when the biopsy is performed. Fine needle aspiration cytology (FNAC) is successfully used in lymph nodes (LNs) in combination with different ancillary techniques and might be used to assess the phenotypic and genetic profile of specific targets and to get key information for therapy, in different phases and stages of the disease, with the option to re‐check the same target over time, without surgical excision. This brief review describes LN‐FNAC diagnostic criteria, current therapies for lymphomas and the potential role of LN‐FNAC in selecting non‐Hodgkin lymphomas patients for specific targeted treatments.

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“…Именно поэтому наряду с поиском новых молекул для химиотерапевтического воздействия активно разрабатываются альтернативные подходы к лечению опухолевых заболеваний. Наиболее пер-спективной является иммунотерапия, включающая моноклональные антитела, ингибиторы контрольных точек иммунного ответа, конъюгаты антител с ци-тотоксическими малыми молекулами, и адоптивная клеточная терапия [5].…”

Section: Introductionunclassified

Manufacturing of CD19 Specific CAR T-Cells and Evaluation of their Functional Activity in Vitro

Петухов¹,

Маркова²,

Моторин³

et al. 2018

Клиническая онкогематология

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Background. The most promising variant of adoptive immunotherapy of the B-line oncohematological diseases includes the use of cells with the chimeric antigen receptor (CAR T-cells), that showed extraordinary results in clinical studies. Aim. To manufacture CAR T-cells for the clinical use and to study their cytotoxicity in vitro. Methods. Human T-lymphocytes were transduced by the lentiviral vector containing anti-CD19-CAR, RIAD, and GFP genes. The T-cell transduction efficacy was assessed on the basis of GFP protein signal by flow cytometry. Propidium iodide was used to analyse the cell viability. Cytotoxic activity of the manufactured CAR T-cells was studied in the presence of the target cells being directly co-cultivated. Analysis of the number and viability of CAR T-cells and cytokine expression was performed by flow cytometry. Results. The viability of the transduced T-cells and GFP expression reached 91.87 % and 50.87 % respectively. When cultured in the presence of IL-2 and recombinant CD19 (the target antigen), the amount of CAR-T after 120 h of the process was 1.4 times larger compared with the period of 48 h. In the cytotoxic test of co-cultivation CART with the K562-CD19+ cells the percentage of CAR-T increased to 57 % and 84.5 % after 48 h and 120 h of exposure respectively. When cultured with the K562 cells (test line not expressing CD19) the number of CAR T-cells decreased to 36.2 % within 48 h while the number of K562 cells increased to 58.3 %. The viability of target cells in the experimental and control groups was 3.5 % and 36.74 % respectively. Comparison of IL-6 level in the control and experimental groups revealed that the differences are insignificant, as opposed to the level of other cytokines (IFN-y, IL-2, TNF) which proved to be different in both groups. Conclusion. The present work resulted in the production of anti-CD19 CAR T-cells with adequate viability. The in vitro model demonstrated their cytotoxicity. Manufacturing of CAR T-cells for clinical use is the first step of the development of adoptive immunotherapy in the Russian Federation.

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Immunotherapy in hematologic malignancies: past, present, and future

Cited by 91 publications

References 86 publications

Macrophages protect mycoplasma‐infected chronic myeloid leukemia cells from natural killer cell killing

Macrophages protect mycoplasma‐infected chronic myeloid leukemia cells from natural killer cell killing

Lymph node fine‐needle cytology in the era of personalised medicine. Is there a role?

Manufacturing of CD19 Specific CAR T-Cells and Evaluation of their Functional Activity in Vitro

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