Combination anti-CD137 and anti-CD40 antibody therapy in murine myc-driven hematological cancers

Westwood, Jennifer A.; Matthews, Geoffrey M.; Shortt, Jake; Faulkner, David; Pegram, Hollie J.; Duong, Connie P.M.; Chesi, Marta; Bergsagel, P. Leif; Sharp, Leslie L.; Huhn, Richard D.; Darcy, Phillip K.; Johnstone, Ricky W.; Kershaw, Michael H.

doi:10.1016/j.leukres.2014.05.010

Cited by 13 publications

(12 citation statements)

References 23 publications

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“…We observed that CD8 + T cells from transplanted mice with progressive myeloma had impaired IFN-γ production, while it was unaffected in those with controlled myeloma. Consistent with this, agonistic CD137 mAb eradicated myeloma in the majority of transplanted animals by increasing Th1/Tc1 expansion, consistent with the known antitumor activity of IFN-γ in cancer models (20,(58)(59)(60). The antimyeloma activity of CD137 agonists has been reported in preclinical nontransplant settings (20,60), and a phase I trial (NCT02252263) has recently been completed, however, no results have been reported to date.…”

Section: Discussionsupporting

confidence: 69%

Bone marrow transplantation generates T cell–dependent control of myeloma in mice

Vučković¹,

Minnie²,

Smith³

et al. 2018

Journal of Clinical Investigation

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Section: Discussionsupporting

confidence: 69%

Bone marrow transplantation generates T cell–dependent control of myeloma in mice

Vučković¹,

Minnie²,

Smith³

et al. 2018

Journal of Clinical Investigation

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“…Targeting 4–1BB co-stimulation has proven to be an effective form of immunomodulation to promote antitumor immunity and potentiate the therapeutic effects of tumor- and immune-targeting antibodies against lymphoma 24,25 , 40 and other cancers. 21,22 In this study we show that anti-4–1BB mAb treatment significantly improves the efficacy of a cellular vaccine strategy that targets the immune adjuvant properties of NKT cells.…”

Section: Discussionmentioning

confidence: 99%

NKT cell-targeted vaccination plus anti-4–1BB antibody generates persistent CD8 T cell immunity against B cell lymphoma

et al. 2015

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Harnessing the immune adjuvant properties of natural killer T (NKT) cells is an effective strategy to generate anticancer immunity. The objective of this study was to increase the potency and durability of vaccine-induced immunity against B cell lymphoma by combining α-galactosylceramide (α-GalCer)-loaded tumor cell vaccination with an agonistic antibody targeting the immune checkpoint molecule 4–1BB (CD137). We observed potent synergy when combining vaccination and anti-4–1BB antibody treatment resulting in significantly enhanced survival of mice harboring Eμ-myc tumors, including complete eradication of lymphoma in over 50% of mice. Tumor-free survival required interferon γ (IFNγ)-dependent expansion of CD8+ T cells and was associated with 4–1BB-mediated differentiation of KLRG1+ effector CD8+ T cells. 'Cured' mice were also resistant to lymphoma re-challenge 80 days later indicating successful generation of immunological memory. Overall, our results demonstrate that therapeutic anticancer vaccination against B cell lymphoma using an NKT cell ligand can be boosted by subsequent co-stimulation through 4–1BB leading to a sustainable immune response that may enhance outcomes to conventional treatment.

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“…Combination therapies can potentiate T cell–based cancer immunotherapy (Table 2). Agonistic CD137 mAbs with anti–CTLA-4 or anti-CD40 mAbs increased the survival of mice injected with MC38 murine colon cancer cells (43, 44). Uno and colleagues (45) reported that an agonistic mAb to death receptor 5 (DR5; also known as TNFRSF10B), the apoptosis-inducing receptor for TNF-related apoptosis-inducing ligand, combined with agonistic mAbs to the costimulatory molecules CD40 and CD137, rapidly stimulated tumor-specific effector CD8 + T cells that led to eradication of preestablished tumors.…”

Section: Preclinical Studies Of Cd137 Antibodymentioning

confidence: 99%

Boosting Cancer Immunotherapy with Anti-CD137 Antibody Therapy

Yonezawa

Dutt

Chester

et al. 2015

Clinical Cancer Research

115

111

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In the past 5 years, immunomodulatory antibodies have revolutionized cancer immunotherapy. CD137, a member of the tumor necrosis factor receptor superfamily, represents a promising target for enhancing antitumor immune responses. CD137 helps regulate the activation of many immune cells, including CD4+ T cells, CD8+ T cells, dendritic cells, and natural killer cells. Recent studies indicate that the antitumor efficacy of therapeutic tumor-targeting antibodies can be augmented by the addition of agonistic antibodies targeting CD137. As ligation of CD137 provides a costimulatory signal in multiple immune cell subsets, combination therapy of CD137 antibody with therapeutic antibodies and/or vaccination has the potential to improve cancer treatment. Recently, clinical trials of combination therapies with agonistic anti-CD137 mAbs have been launched. In this review, we discuss the recent advances and clinical promise of agonistic anti-CD137 monoclonal antibody therapy.

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Combination anti-CD137 and anti-CD40 antibody therapy in murine myc-driven hematological cancers

Cited by 13 publications

References 23 publications

Bone marrow transplantation generates T cell–dependent control of myeloma in mice

Bone marrow transplantation generates T cell–dependent control of myeloma in mice

NKT cell-targeted vaccination plus anti-4–1BB antibody generates persistent CD8 T cell immunity against B cell lymphoma

Boosting Cancer Immunotherapy with Anti-CD137 Antibody Therapy

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