One of the primary ways the Edmonstron strain of measles virus attacks human cells in through interaction with a human protein called CD46.

It just so happens that, in myeloma, cancer cells express lots and lots of CD46. So when a patient is injected with the attenuated Edmonstron MV-NIS dose, the virus goes straight to the cancer sites where the CD46 receptor is readily available.

Medulloblastoma (a malignant brain tumor common in childhood) specimens also express lots of CD46, so the high-dose measles vaccine is also very effective at targeting those tumors.

In both patients, the virus, at a dose of 10¹¹ TCID₅₀, was infused into a superficial arm vein in 100 mL of normal saline over 60 minutes. TCID₅₀ is the amount of a viral agent necessary to produce pathological change in 50% of cell cultures inoculated. The patients were injected with 100 trillion times that amount.

This is a dose high enough to vaccinate 10 million people against measles.

MV-NIS stands for Measles Virus encoding Na/Iodide Symporter.

MV-NIS is a recombinant oncolytic measles virus derived from an attenuated Edmonston lineage vaccine strain (MV-Edm) that was adapted to grow on human cancer (HeLa) cells (learn more about HeLa cells here). These viruses were then genetically engineered to express the human thyroidal sodium iodide symporter (NIS). This expression acts as a marker so that the viral spread inside te patient can be noninvasively monitored by radioiodine single-photon emission computed tomography (SPECT) imaging.

“Planet Rock” is an early 1980s Afrika Bambaataa song.

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Though, as scientists, the authors of this paper strive to document observations and draw conclusions objectively, it is ethical to be forthcoming and disclose these potential competing interests so the audience is aware of any possible bias that might have crept into the research process.

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Patient 2 was a 65-year-old woman with relapsing IgA κ MM refractory to all approved antimyeloma drugs who experienced disease progression while receiving carfilzomib, pomalidomide, and dexamethasone therapy. Her MM had been diagnosed 7 years earlier and had been treated with local radiotherapy; high-dose dexamethasone; lenalidomide and dexamethasone; single-agent bortezomib; cyclophosphamide, bortezomib, and dexamethasone; ASCT; lenalidomide, bendamustine, and dexamethasone; bortezomib, cyclophosphamide, lenalidomide, and dexamethasone; carfilzomib plus dexamethasone; bortezomib, dexamethasone, thalidomide, cisplatin, doxorubicin, cyclophosphamide, and etoposide; and several experimental therapies. Before MV-NIS therapy, she had innumerable palpable (firm, nontender) soft tissue plasmacytomas, especially in the muscles of her lower extremities, ranging in diameter from 2 to 7 cm. Her hemoglobin level was 8.9 g/dL (to convert to g/L, multiply by 10), and her serum κ free light chain value had increased from 6.5 mg/dL to 31.1 mg/dL (to convert to mg/L, multiply by 10) over the previous month. PET-CT revealed numerous fluorodeoxyglucose (FDG)–avid nodules and mass lesions, most prominent below the level of the diaphragm and especially in the soft tissues of the legs. Several of these lesions had increased in size and FDG activity since the previous scan 6 weeks earlier. The largest lesion, located in the left hamstring musculature, measured 74 × 46 mm with a maximum standard uptake value of 8.0. Bone marrow biopsy revealed 1% infiltration with κ light chain–restricted clonal plasma cells.

Patient 1 was a 49-year-old woman with heavily pretreated light chain MM who experienced relapse while receiving no therapy 9 months after her second autologous stem cell transplant (ASCT). Multiple myeloma had been diagnosed 9 years earlier and treated with thalidomide and dexamethasone followed by consolidative ASCT12; lenalidomide and dexamethasone13; cyclophosphamide, bortezomib, and dexamethasone14; and a second ASCT.

Read the full HTML paper, published on 05/13/14, here.

Proof of principle (sometimes referred to as proof of concept) clinical trials are studies done on humans to determine the safety of a compound or therapy after it has already demonstrated potential in early safety testing and animal models.

These studies are usually conducted on a very small scale and are designed to spot evidence of efficacy. They often link Phase I and Phase II of clinical trials.