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  • Poster presentation
  • Open Access

Activation of innate and adaptive immunity as an effective combined strategy for cancer immunotherapy

  • 1,
  • 1,
  • 1,
  • 1,
  • 2,
  • 3 and
  • 4
Journal for ImmunoTherapy of Cancer20153 (Suppl 2) :P370

https://doi.org/10.1186/2051-1426-3-S2-P370

  • Published:

Keywords

  • Antitumor Effect
  • Adaptive Immunity
  • Drain Lymph Node
  • Cancer Immunotherapy
  • Intratumoral Injection

Immunotherapeutic approaches can demonstrate some antitumor benefit, but their efficacy is limited when they are used as a single modality. We asked if a combinatory approach activating both innate and adaptive immunity would improve cancer immunotherapy. We have previously shown that an agonistic anti-CD40 monoclonal antibody (anti-CD40) in combination with a toll-like receptor 9 agonist, CpG, can activate macrophages in mice, leading to tumor cell killing. Separately, we have shown that a direct intratumoral injection of an immunocytokine (IC) consisting of anti-GD2 antibody linked to interleukin-2 can activate NK and T cells, resulting in antitumor effects. We hypothesize that activation of macrophages (with anti-CD40/CpG) and NK cells (with IC) will increase tumor destruction and presentation of tumor antigens, leading to T cell activation, which in turn could be further augmented by anti-CTLA-4 antibody, resulting in tumor eradication and prevention of tumor recurrence. Using the mouse GD2+ B78 melanoma model, we show that anti-CD40/CpG and IC/anti-CTLA-4 synergistically induced regression of established subcutaneous tumors, resulting in the cure of 50% of mice and development of immunological memory against B78 as well as wild type B16 tumors. While the antitumor effect of anti-CD40/CpG was T cell independent, the antitumor effect of IC/anti-CTLA-4 required T cells. Anti-CD40/CpG treatment led to upregulation of T cell activation markers in draining lymph nodes. Finally, the combined treatment with anti-CD40/CpG and IC/anti-CTLA-4 was effective against B16 lung metastases. We suggest that a combination of anti-CD40/CpG and IC/anti-CTLA-4 should be tested as a clinically relevant novel treatment strategy.

Authors’ Affiliations

(1)
UW-Madison, Madison, WI, USA
(2)
Bristol-Myers Squibb Company, Redwood City, CA, USA
(3)
Provenance Biopharmaceuticals, Carlisle, MA, USA
(4)
Department of Human Oncology, Department of Pediatrics, University of Wisconsin-Madison, Madison, WI, USA

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