Biomaterials and emerging anticancer therapeutics: engineering the microenvironment

Abstract

The microenvironment is increasingly recognized to have key roles in cancer, and biomaterials provide a means to engineer microenvironments both in vitro and in vivo to study and manipulate cancer. In vitro cancer models using 3D matrices recapitulate key elements of the tumour microenvironment and have revealed new aspects of cancer biology. Cancer vaccines based on some of the same biomaterials have, in parallel, allowed for the engineering of durable prophylactic and therapeutic anticancer activity in preclinical studies, and some of these vaccines have moved to clinical trials. The impact of biomaterials engineering on cancer treatment is expected to further increase in importance in the years to come.

Figure 1. Creating new microenvironments in vitro and in vivo using biomaterials

Biomaterials are being used to both create 3D in vitro cancer models that mimic the microenvironmental conditions found in tumors, and to create new microenvironments within the body to allow effective immune cell activation and anti-tumor function. Knowledge gained from studies with 3D in vitro models can inform design of therapeutic biomaterials, while clinical experience resulting from use of biomaterials in vivo can inform the design of new 3D models that more faithfully mimic in vivo biology.

Figure 2. Biomaterials to create 3D in vitro human tumor models

a) Engineered 3D in vitro tumor models recapitulate various microenvironmental cues of human tumors. b) 3D in vitro tumor models can be used to screen anticancer therapeutics as various microenvironmental conditions are modulated, to determine the impact of each condition on efficacy of the therapeutic approach.

Figure 3. Biomaterials-based cancer immunotherapies

a) Biomaterial-based cancer vaccines. In one approach (left panel), a scaffold releases recruiting factors (e.g. GM-CSF) from the vaccine into surrounding tissue to direct host DCs to migrate into the device, where the DCs are exposed to tumor antigens and “danger signals” (e.g. CpG) that activate the DCs, and enable their homing to lymph nodes to elicit a cytotoxic T lymphocyte (CTL) anti-tumor response. Alternatively (right panel), nanoparticles are used to target DCs in lymph nodes, and deliver antigens and “danger signals” to again generate a CTL response. b) Biomaterial-based T cell manipulation. Either scaffolds (left panel), or nano- or micro-particles (right panel) are used to provide a stimulatory microenvironment to T cells for ACT in order to expand T cells and maintain their activity against tumors.