Inhaled Viral Capsids Trigger Systemic Antitumor Response in Mouse Model

The shells of deactivated Cowpea mosaic virus (CPMV) were found have potent adjuvant activity on cancer growth, which was demonstrated by the ability to block immune system suppression in the tumor microenvironment and subsequently to trigger a full-blown systemic antitumor immune response.

The "in situ vaccination" immunotherapy strategy postulates the direct manipulation of tumors to overcome local tumor-mediated immunosuppression and subsequently stimulate systemic antitumor immunity to treat metastases.

As a test of this strategy, investigators at Dartmouth College (Hanover, NH, USA) and their colleagues at Case Western Reserve University (Cleveland, OH, USA) treated mice with lung melanomas with self-assembling virus-like nanoparticles from CPMV.

CPMV's genetic, biological, and physical properties are well characterized, and it can be isolated readily from plants. There are many stable mutants already prepared that allow specific modification of the capsid surface. It is possible to attach a number of different chemicals to the virus surface and to construct multilayer arrays of such nanoparticles on solid surfaces. This gives the natural or genetically engineered nanoparticles a range of properties which could be useful in nanotechnological applications. Furthermore, CPMV nanoparticles are stable, nontoxic, modifiable with drugs and antigens, and their nanomanufacture is highly scalable.

The investigators reported in the December 21, 2015, online edition of the journal Nature Nanotechnology that inhalation of CPMV nanoparticles by mice reduced the size of established B16F10 lung melanoma tumors and simultaneously generated potent systemic antitumor immunity against poorly immunogenic B16F10 introduced into the skin. Full potency required interleukin-12 (IL-12), (interferon-gamma) IFN-gamma, adaptive immunity, and neutrophils. Inhaled CPMV nanoparticles were rapidly taken up by and activated neutrophils in the tumor microenvironment as an important part of the antitumor immune response.

CPMV also exhibited clear treatment efficacy and systemic antitumor immunity in ovarian, colon, and breast tumor models in multiple anatomic locations.

"The particles are shockingly potent," said senior author Dr. Steven Fiering, professor of microbiology and immunology at Dartmouth College. "They are easy to make and do not need to carry antigens, drugs, or other immunestimulatory agents on their surface or inside. Because everything we do is local, the side effects are limited, and despite the strength and extent of the immune response no toxicity was found."

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Dartmouth College
Case Western Reserve University