Multivalent bi-specific nanobioconjugate engagerfor targeted cancer immunotherapy

Nature Nanotechnology 2017, Vol 12, p763

by Betty Kim from the Mayo Clinic

Supported almost entirely by internally funding through the Mayo Clinic

Abstract: Tumour-targeted immunotherapy offers the unique advantageof specific tumouricidal effects with reduced immune-associated toxicity. However, existing platforms suffer from low potency, inability to generate long-term immune memory anddecreased activities against tumour-cell subpopulations withlow targeting receptor levels. Here we adopted a modular design approach that uses colloidal nanoparticles as substrates to create a multivalent bi-specific nanobioconjugate engager (mBiNE) to promote selective, immune-mediated eradicationof cancer cells. By simultaneously targeting the human epidermal growth factor receptor 2 (HER2) expressed by cancer cells and pro-phagocytosis signalling mediated by calreticulin, the mBiNE stimulated HER2-targeted phagocytosis and produceddurable antitumour immune responses against HER2-expressing tumours. Interestingly, although the initial immune acti-vation mediated by the mBiNE was receptor dependent, thesubsequent antitumour immunity also generated protectiveeffects against tumour-cell populations that lacked the HER2 receptor. Thus, the mBiNE represents a new targeted, nanomaterial-immunotherapy platform to stimulate innate and adaptive immunity and promote a universal antitumour response.

Innate immunity: macrophage response

Adaptive immunity: T-cell response and generation

Summary: Kim has developed and confirmed the development of a novel method to treat cancer tumors via the general immunotherapy method. They activated both the innate and adaptive immune response of the body using their nanoparticles to promote both quick cancer removal by macrophage cell engulfment and by immune cell recognition and long term removal. The novelty here is the activation of both responses in mice using a versatile nanoparticle formulation.

Business Development: While they demonstrated excellent efficacy in a mouse breast cancer model, there are so many major hurdles to overcome. I would anticipate, based on how they are preparing and delivering their formulation, that manufacturing and safety profiles will be the next items to work on. As with all nanoparticle formulations used for medical applications, excessive particle characterization will be required. Since the authors have already patented their nanoparticle formulation, I would anticipate that they will begin conducting these tests internally until which time they can remove more of the risk and spin out a company.