Co-infusion of high-dose haploidentical donor cells and CD19-targeted CART cells achieves complete remission, successful donor engraftment and significant CART amplification in advanced ALL

Autologous CD19-targeted chimeric antigen receptor-modified T cells (CD19-CART) remarkably improved the outcome of patients with advanced B-cell acute lymphoblastic leukemia (B-ALL). However, the application and outcomes of allogeneic CART cells is still uncertain. Two patients with advanced B-ALL were enrolled to receive a co-infusion of high-dose human leukocyte antigen-haploidentical donor granulocyte colony-stimulating factor mobilized peripheral blood mononuclear cells (GPBMCs; 21.01–25.34 × 108/kg) and the same donor-derived CD19-targeted CART cells (8.44–22.19 × 106/kg) without additional in vitro gene-editing following a reinduction chemotherapy as precondition. They achieved complete remission and full donor chimerism (FDC) with ongoing 20- and 4-month leukemia-free survival. A significant amplification of donor CART cells was detected in peripheral blood and/or cerebrospinal fluid and was associated with the formation of FDC. The highest amount of copies of the donor CART cells reached 4962 per µg of genomic DNA (gDNA) and 2449 per µg of gDNA, and the longest persistence was 20 months associated with B cell aplasia. Two patients experienced Grade II or III cytokine release syndromes and developed controllable Grade II intestinal acute graft-versus-host disease (GVHD) or limited chronic oral GVHD. High-dose donor GPBMC infusion may enhance amplification and persistence of haploidentical CD19-targeted CART cells, suggesting an alternative therapy for advanced B-ALL patients.

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Persistent augmentation of natural-killer- and T-cell-mediated cytotoxicity in peripheral blood mononuclear cells pulsed in vitro with high-dose recombinant interleukin-2 prior to culturing with a low maintenance dose

Cancer Immunology Immunotherapy ◽

10.1007/s002620050091 ◽

1994 ◽

Vol 39 (1) ◽

pp. 34-40

Author(s):

P. A. Palmer ◽

J. G. M. Scharenberg ◽

B. M. E. von Blomberg ◽

A. G. M. Stam ◽

C. J. L. M. Meijer ◽

...

Keyword(s):

Peripheral Blood Mononuclear Cells ◽

Peripheral Blood ◽

Maintenance Dose ◽

Mononuclear Cells ◽

Interleukin 2 ◽

High Dose ◽

Peripheral Blood Mononuclear ◽

Blood Mononuclear Cells ◽

Recombinant Interleukin 2

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Curcumin and EGCG Suppress Apurinic/Apyrimidinic Endonuclease 1 and Induce Complete Remission in B-cell Non-Hodgkin's lymphoma Patients

Functional Foods in Health and Disease ◽

10.31989/ffhd.v1i12.108 ◽

2011 ◽

Vol 1 (12) ◽

pp. 525 ◽

Cited By ~ 5

Author(s):

Ahmad R. Bassiouny ◽

Mona A. Atteya ◽

Fatma H. El-Rashidy ◽

Hashem M. Neenaa

Keyword(s):

Complete Remission ◽

Follicular Lymphoma ◽

B Cell ◽

Green Tea ◽

Peripheral Blood Mononuclear Cells ◽

Peripheral Blood ◽

Mononuclear Cells ◽

Peripheral Blood Mononuclear ◽

Chemopreventive Agents ◽

Blood Mononuclear Cells

Background: Follicular lymphoma (FL) is the most common subtype of indolent lymphoma. FL is still considered to be an incurable disease and palliation of symptoms is an acceptable approach to the expected pattern of repeated relapses due to developing resistance to chemotherapy agents. Apurinic/apyrimidinic endonuclease/redox factor-1 (APE1/Ref-1) is a multifunctional protein involved in DNA base excision repair (BER) of oxidative DNA damage and in redox regulation of a number of transcription factors. It was observed that cytoplasmic APE1 induced COX-2 expression through NF-κB activation. It has been shown that chemopreventive agents potentiate the efficacy of chemotherapy through the regulation of multiple signaling pathways, including NF-κB, c-Myc, cyclooxygenase-2, apoptosis, and others, suggesting a multitargeted nature of chemopreventive agents. We hypothesized that curcumin, a polyphenolic antioxidant derived from the spice turmeric, and epigallocatechin gallate (EGCG) from green tea would potentiate the effect of chemotherapy in B-cell lymphoma.Objective: We examined the role of human apurinic/apyrimidinic endonuclease 1 (APE1) in resistance and prognosis in patients with FL. Our major objective was to update the safety and efficacy results of the antitumor effect of combination of curcumin and EGCG therapy in relapsed or resistant indolent or transformed non-Hodgkin follicular lymphoma patients and their peripheral blood mononuclear cells (PBMCs) compared with healthy donors’ controls. Methods: Thirty patients with FL with over-expression of constitutive active NF-κB in their PBMCs received regular CHOP and consumed capsules compatible with curcumin doses between 0.9 and 5.4 g daily for up to 9 months and 9.0 g/day green tea whole extract "1000 mg tablets of green tea whole extract containing 200 mg EGCG. We designed a dose-escalation study to explore the efficacy of CHOP in combination with curcumin and the green tea extract epigallocatechin-3 gallate (EGCG) on the viability of patients’ peripheral blood mononuclear cells (PBMCs) lymphocytes. Results: Treatment of patients with the combination of curcumin and EGCG, significantly lower cytoplasmic APE1 and the levels of the transcription factor were lower than those predicted from the effects of the CHOP agents (cyclophosphamide, doxorubicin, vincristine, and prednisone) alone, especially with a blunting of the remarkable increases in NF- κB activation induced by CHOP. Eighteen of the patients had a CR (18/30), and twelve patients had PR (12/30) within 9 month treatment and followed up to 12 months. They remain disease-free a mean of 8.6 y (range, 7.9–9.2 y) after this combination therapy.Conclusion: Optimal patient benefit might be obtained in follicular lymphoma when administering curcumin up-front in combination with chemotherapy and EGCG treatment. The combination of curcumin with EGCG resulted in a synergistic antitumor activity and that with CHOP agents in additivity or sub-additivity, down-regulated the expression of all NF-κB regulated gene products, leading to the suppression of angiogenesis, metastasis and entering in complete remission as indicated by β2-microglobulin and lactate dehydrogenase (LDH) levels. Key words: Curcumin, EGCG, B- cell NHL, NF-κB, VEGF, APE1, lymphoma

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Persistent augmentation of natural-killer-and T-cell-mediated cytotoxicity in peripheral blood mononuclear cells pulsed in vitro with high-dose recombinant interleukin-2 prior to culturing with a low maintenance dose

Cancer Immunology Immunotherapy ◽

10.1007/bf01517178 ◽

1994 ◽

Vol 39 (1) ◽

pp. 34-40

Author(s):

P. A. Palmer ◽

J. G. M. Scharenberg ◽

B. M. E. von Blomberg ◽

A. G. M. Stam ◽

C. J. L. M. Meijer ◽

...

Keyword(s):

Peripheral Blood Mononuclear Cells ◽

Peripheral Blood ◽

Maintenance Dose ◽

Mononuclear Cells ◽

Interleukin 2 ◽

High Dose ◽

Peripheral Blood Mononuclear ◽

Blood Mononuclear Cells ◽

Recombinant Interleukin 2

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The effects of Malassezia on pro-inflammatory cytokine production by human peripheral blood mononuclear cells in vitro

Medical Mycology ◽

10.1046/j.1365-280x.1998.00137.x ◽

1998 ◽

Vol 36 (2) ◽

pp. 97-106 ◽

Cited By ~ 6

Author(s):

S. KESAVAN ◽

C. E. WALTERS ◽

K. T. HOLLAND ◽

E. INGHAM

Keyword(s):

Peripheral Blood Mononuclear Cells ◽

Peripheral Blood ◽

Inflammatory Cytokine ◽

Mononuclear Cells ◽

Cytokine Production ◽

Human Peripheral Blood ◽

Peripheral Blood Mononuclear ◽

Inflammatory Cytokine Production ◽

Blood Mononuclear Cells

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CD8+ T cells from feline immunodeficiency virus (FIV) infected cats suppress exogenous FIV replication of their peripheral blood mononuclear cells in vitro

Archives of Virology ◽

10.1007/s00705-002-0827-1 ◽

2002 ◽

Vol 147 (8) ◽

pp. 1517-1529 ◽

Cited By ~ 14

Author(s):

T. Hohdatsu ◽

T. Sasagawa ◽

A. Yamazaki ◽

K. Motokawa ◽

H. Kusuhara ◽

...

Keyword(s):

T Cells ◽

Peripheral Blood Mononuclear Cells ◽

Cd8 T Cells ◽

Feline Immunodeficiency Virus ◽

Peripheral Blood ◽

Mononuclear Cells ◽

Peripheral Blood Mononuclear ◽

Immunodeficiency Virus ◽

Blood Mononuclear Cells

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Potential Role and Impact of Peripheral Blood Mononuclear Cells in Radiographic Axial Spondyloarthritis-Associated Endothelial Dysfunction

Diagnostics ◽

10.3390/diagnostics11061037 ◽

2021 ◽

Vol 11 (6) ◽

pp. 1037

Author(s):

Patricia Ruiz-Limon ◽

Maria L. Ladehesa-Pineda ◽

Clementina Lopez-Medina ◽

Chary Lopez-Pedrera ◽

Maria C. Abalos-Aguilera ◽

...

Keyword(s):

Endothelial Dysfunction ◽

Peripheral Blood Mononuclear Cells ◽

Peripheral Blood ◽

Mononuclear Cells ◽

Axial Spondyloarthritis ◽

Endothelial Injury ◽

In Vitro Studies ◽

Peripheral Blood Mononuclear ◽

Blood Mononuclear Cells

Endothelial dysfunction (ED) is well known as a process that can lead to atherosclerosis and is frequently presented in radiographic axial spondyloarthritis (r-axSpA) patients. Here, we investigated cellular and molecular mechanisms underlying r-axSpA-related ED, and analyzed the potential effect of peripheral blood mononuclear cells (PBMCs) in promoting endothelial injury in r-axSpA. A total of 30 r-axSpA patients and 32 healthy donors (HDs) were evaluated. The endothelial function, inflammatory and atherogenic profile, and oxidative stress were quantified. In vitro studies were designed to evaluate the effect of PBMCs from r-axSpA patients on aberrant endothelial activation. Compared to HDs, our study found that, associated with ED and the plasma proatherogenic profile present in r-axSpA, PBMCs from these patients displayed a pro-oxidative, proinflammatory, and proatherogenic phenotype, with most molecular changes noticed in lymphocytes. Correlation studies revealed the relationship between this phenotype and the microvascular function. Additional in vitro studies confirmed that PBMCs from r-axSpA patients promoted endothelial injury. Altogether, this study suggests the relevance of r-axSpA itself as a strong and independent cardiovascular risk factor, contributing to a dysfunctional endothelium and atherogenic status by aberrant activation of PBMCs. Lymphocytes could be the main contributors in the development of ED and subsequent atherosclerosis in this pathology.

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