Blockade of PD-1 in Combination with Dendritic Cell/Myeloma Fusion Cell Vaccination Following Autologous Stem Cell Transplantation

Rosenblatt, Jacalyn; Avivi, Irit; Vasir, David; Uhl, Lynne; Katz, Tamar; Somaiya, Poorvi; Mills, Heidi; Joyce, Robin; Levine, James D.; Boussiotis, Vassiliki A.; Luptakova, Katarina; Arnason, Jon; Drummy, Natalie; Delaney, Carol; Breault, Emma; Held, Viki; Bisharat, Lina; Giallombardo, Nancy; Mortellite, Jamie; Wagoner, Judith; Schickler, Michael; Rotem-Yehudar, Rinat; Richardson, Paul G.; Laubach, Jacob P.; Anderson, Kenneth C.; Munshi, Nikhil C.; Rowe, Jacob M.; Küfe, Donald; Avigan, David

doi:10.1016/j.bbmt.2012.11.021

Cited by 11 publications

(12 citation statements)

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“…In the CT-011 alone cohort, a dramatic and persistent expansion of myelomaspecific T cells was noted. 63 Transplant and immunotherapy for myeloma N Lendvai et al…”

Section: Myeloma Vaccinesmentioning

confidence: 99%

Beyond consolidation: auto-SCT and immunotherapy for plasma cell myeloma

Lendvai

Cohen

Cho

2015

Bone Marrow Transplant

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Autologous hematopoietic cell transplantation (auto-HCT) is the standard consolidation therapy for plasma cell myeloma patients following induction therapy. Auto-HCT improves disease-free survival (DFS), but is generally not curative. The allogeneic HCT experience demonstrated that T-cell immunotherapy can confer long-term DFS. Preclinical and clinical data indicate that myelomaassociated Ags elicit humoral and cellular immune responses (IRs) in myeloma patients. These findings strongly suggest that the immunotherapeutic strategies, including immune checkpoint inhibitors, therapeutic cancer vaccines and adoptive cellular therapies, are promising avenues of clinical research that may be most applicable in the minimal residual disease state following auto-HCT. These strategies are designed to prime or augment antimyeloma IRs and promote a 'host-vs-myeloma' effect that may result in durable DFS. Innovative clinical trials investigating immune checkpoint inhibitors and cancer vaccines have demonstrated that robust immunity against myeloma-associated Ags can be elicited in the setting of auto-HCT. A diverse array of immunotherapeutic strategies have entered clinical trials in myeloma, including PD-1/PD-L1 inhibitors, DC/myeloma cell fusion vaccines and adoptive chimeric Ag receptor T-cell therapy, and further investigation of combinations of immunologic and pharmaceutical agents are expected in the near future. In this review, we will discuss the preclinical data supporting immunotherapy in auto-HCT for myeloma, clinical investigation of these strategies and the future prospects of immunotherapy in pursuit of the goal of curative therapy.

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“…In the CT-011 alone cohort, a dramatic and persistent expansion of myelomaspecific T cells was noted. 63 Transplant and immunotherapy for myeloma N Lendvai et al…”

Section: Myeloma Vaccinesmentioning

confidence: 99%

Beyond consolidation: auto-SCT and immunotherapy for plasma cell myeloma

Lendvai

Cohen

Cho

2015

Bone Marrow Transplant

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“…Already 22 RRMM patients have been enrolled, 27% (6/22) of them reached VGPR, another 27% (6/22) CR, although these results must be interpreted with caution, as it is not clear what kind of treatment is responsible for the outcomes. 39 Briefly, two randomized phase 3 clinical trials examine the efficacy of pembrolizumab. Pomalidomide C dexamethasone vs. pomalidomide C dexamethasone C pembrolizumab in RRMM patients is compared in KEYNOTE-183, whereas the combination of lenalidomide and dexamethasone with or without pembrolizumab in NDMM is tested in KEYNOTE-185 (30).…”

Section: Nivolumabmentioning

confidence: 99%

PD-1/PD-L1 inhibitors in multiple myeloma: The present and the future

Jelı́nek

2016

OncoImmunology

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The introduction of PD-1/PD-L1 pathway inhibitors has marked a significant milestone in the treatment of various types of solid tumors. The current situation in multiple myeloma (MM) is rather unclear, as distinct research groups have reported discordant results. This discrepancy dominantly concerns the expression of PD-1/PD-L1 molecules as well as the identification of the responsible immune effector cell population. The results of monotherapy with PD-1/PD-L1 inhibitors have been unsatisfactory in MM, suggesting that a combination approach is needed. The most logical partners are immunomodulatory agents as they possess many synergistic effects. We are also proposing other rational and promising combinations (e.g., daratumumab, ibrutinib, anti-CD137) that warrant further investigation.

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“…As a treatment for follicular lymphoma, the enhancement of antitumor CD8+ T-cell responses is the goal of a Phase II trial (NCT02677155) combining anti-PD-1 antibody administration with sequential intranodal immunotherapy using rituximab (anti-CD20 antibody) and DCs plus radiotherapy. An autologous DC/myeloma fusion vaccine stimulates more robust antitumor T-cell responses when combined with anti-PD-1 antibody in vitro [18], with a clinical trial (NCT01067287) integrating PD-1 blockade following DC/myeloma vaccination promoting increased frequencies of tumor-reactive CD8 + T cells and reduced frequencies of Treg in patient peripheral blood, with complete responses noted in a subset of treated patients [19]. Phase II trials examining blockade of PD-1 in conjunction with DC-tumor cell fusion-based vaccines are ongoing for the treatment of acute myelogenous leukemia and kidney cancer (NCT01096602, NCT01441765).…”

Section: Targeting Checkpoint Pathwaysmentioning

confidence: 99%

Combination Strategies to Enhance the Potency of Monocyte-Derived Dendritic Cell-Based Cancer Vaccines

Fecek

Storkus

2016

Immunotherapy

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Dendritic cells (DCs) are potent inducers of adaptive immunity and their clinical use in cancer vaccine formulations remains an area of active translational and clinical investigation. Although cancer vaccines applied as monotherapies have had a modest history of clinical success, there is great enthusiasm for novel therapeutic strategies combining DC-based cancer vaccines with agents that 'normalize' immune function in the tumor microenvironment (TME). Broadly, these combination vaccines are designed to antagonize/remove immunosuppressive networks within the TME that serve to limit the antitumor action of vaccine-induced T cells and/or to condition the TME to facilitate the recruitment and optimal function and durability of vaccine-induced T cells. Such combination regimens are expected to dramatically enhance the clinical potency of DC-based cancer vaccine platforms.

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Blockade of PD-1 in Combination with Dendritic Cell/Myeloma Fusion Cell Vaccination Following Autologous Stem Cell Transplantation

Cited by 11 publications

References 0 publications

Beyond consolidation: auto-SCT and immunotherapy for plasma cell myeloma

Beyond consolidation: auto-SCT and immunotherapy for plasma cell myeloma

PD-1/PD-L1 inhibitors in multiple myeloma: The present and the future

Combination Strategies to Enhance the Potency of Monocyte-Derived Dendritic Cell-Based Cancer Vaccines

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