Novel strategies of adoptive immunotherapy: How natural killer cells may change the treatment of elderly patients with acute myeloblastic leukemia

Lemoli, Roberto M.; Parisi, Sarah; Curti, Antonio

doi:10.1016/j.exphem.2016.10.007

Cited by 5 publications

(5 citation statements)

References 41 publications

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“…Thus, our data support the notion that lymphocyte repletion and CI treatment early post-ASCT may accelerate the NK cell development/maturation and lead to a rapid accumulation of mature NK cells, which may exert anti-neoplastic activity as shown in the allo-transplant setting and following conventional immunosuppressive chemotherapy (41)(42)(43)(44). In addition, we show that this setting may favor the expansion of the "adaptive" NK cell compartment in treated patients with a seropositivity status for HCMV, in the absence of HCMV reactivation.…”

Section: Discussionsupporting

confidence: 82%

Post-Transplant Nivolumab Plus Unselected Autologous Lymphocytes in Refractory Hodgkin Lymphoma: A Feasible and Promising Salvage Therapy Associated With Expansion and Maturation of NK Cells

et al. 2021

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Immune checkpoint inhibitors (CI) have demonstrated clinical activity in Hodgkin Lymphoma (HL) patients relapsing after autologous stem cell transplantation (ASCT), although only 20% complete response (CR) rate was observed. The efficacy of CI is strictly related to the host immune competence, which is impaired in heavily pre-treated HL patients. Here, we aimed to enhance the activity of early post-ASCT CI (nivolumab) administration with the infusion of autologous lymphocytes (ALI). Twelve patients with relapse/refractory (R/R) HL (median age 28.5 years; range 18-65), underwent lymphocyte apheresis after first line chemotherapy and then proceeded to salvage therapy. Subsequently, 9 patients with progressive disease at ASCT received early post-transplant CI supported with four ALI, whereas 3 responding patients received ALI alone, as a control cohort. No severe adverse events were recorded. HL-treated patients achieved negative PET scan CR and 8 are alive and disease-free after a median follow-up of 28 months. Four patients underwent subsequent allogeneic SCT. Phenotypic analysis of circulating cells showed a faster expansion of highly differentiated NK cells in ALI plus nivolumab-treated patients as compared to control patients. Our data show anti-tumor activity with good tolerability of ALI + CI for R/R HL and suggest that this setting may accelerate NK cell development/maturation and favor the expansion of the “adaptive” NK cell compartment in patients with HCMV seropositivity, in the absence of HCMV reactivation.

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Section: Discussionsupporting

confidence: 82%

Post-Transplant Nivolumab Plus Unselected Autologous Lymphocytes in Refractory Hodgkin Lymphoma: A Feasible and Promising Salvage Therapy Associated With Expansion and Maturation of NK Cells

et al. 2021

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“…In conclusion, with an extended follow-up of 55.5 months, we point out that an adequate dose of adoptively transferred alloreactive NK cells has the potential to induce a durable control of AML in elderly patients who are unfit for allogeneic stem cell transplantation. Furthermore, the present long-term analysis reinforces the concept that the frequency of NK cells in the infused product may be considered a marker with a predictive value for the clinical outcome (11). The possibility of infusing a number of functionally active NK cells is likely to have a greater impact on the efficacy of NK infusion than simply enumerating the number of total NK cells.…”

Section: Resultssupporting

confidence: 73%

Long-Term Outcome After Adoptive Immunotherapy With Natural Killer Cells: Alloreactive NK Cell Dose Still Matters

et al. 2022

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Recently, many reports were published supporting the clinical use of adoptively transferred natural killer (NK) cells as a therapeutic tool against cancer, including acute myeloid leukemia (AML). Our group demonstrated promising clinical response using adoptive immunotherapy with donor-derived alloreactive KIR-ligand-mismatched NK cells in AML patients. Moreover, the antileukemic effect was correlated with the dose of infused alloreactive NK cells (“functional NK cell dose”). Herein, we update the results of our previous study on a cohort of adult AML patients (median age at enrollment 64) in first morphological complete remission (CR), not eligible for allogeneic stem cell transplantation. After an extended median follow-up of 55.5 months, 8/16 evaluable patients (50%) are still off-therapy and alive disease-free. Overall survival (OS) and disease-free survival (DFS) are related with the dose of infused alloreactive NK cells (≥2 × 105/kg).

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“…Several investigations have addressed the concept of “optimal dose” of NK cells in adoptive transfer immunotherapy [101]. The principal confounding factor is the highly variable number of alloreactive NK cells that can be sourced from each donor.…”

Section: Allogeneic Nk Cell Immunotherapymentioning

confidence: 99%

Natural Killer Cells as Allogeneic Effectors in Adoptive Cancer Immunotherapy

Lupo

Matosevic

2019

Cancers

156

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Natural killer (NK) cells are attractive within adoptive transfer settings in cancer immunotherapy due to their potential for allogeneic use; their alloreactivity is enhanced under conditions of killer immunoglobulin-like receptor (KIR) mismatch with human leukocyte antigen (HLA) ligands on cancer cells. In addition to this, NK cells are platforms for genetic modification, and proliferate in vivo for a shorter time relative to T cells, limiting off-target activation. Current clinical studies have demonstrated the safety and efficacy of allogeneic NK cell adoptive transfer therapies as a means for treatment of hematologic malignancies and, to a lesser extent, solid tumors. However, challenges associated with sourcing allogeneic NK cells have given rise to controversy over the contribution of NK cells to graft-versus-host disease (GvHD). Specifically, blood-derived NK cell infusions contain contaminating T cells, whose activation with NK-stimulating cytokines has been known to lead to heightened release of proinflammatory cytokines and trigger the onset of GvHD in vivo. NK cells sourced from cell lines and stem cells lack contaminating T cells, but can also lack many phenotypic characteristics of mature NK cells. Here, we discuss the available published evidence for the varying roles of NK cells in GvHD and, more broadly, their use in allogeneic adoptive transfer settings to treat various cancers.

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Novel strategies of adoptive immunotherapy: How natural killer cells may change the treatment of elderly patients with acute myeloblastic leukemia

Cited by 5 publications

References 41 publications

Post-Transplant Nivolumab Plus Unselected Autologous Lymphocytes in Refractory Hodgkin Lymphoma: A Feasible and Promising Salvage Therapy Associated With Expansion and Maturation of NK Cells

Post-Transplant Nivolumab Plus Unselected Autologous Lymphocytes in Refractory Hodgkin Lymphoma: A Feasible and Promising Salvage Therapy Associated With Expansion and Maturation of NK Cells

Long-Term Outcome After Adoptive Immunotherapy With Natural Killer Cells: Alloreactive NK Cell Dose Still Matters

Natural Killer Cells as Allogeneic Effectors in Adoptive Cancer Immunotherapy

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