Artificial cells as a novel approach to gene therapy - Artificial Cells, Cell Engineering and Therapy - page 261

weeks in a mouse melanoma model (Cirone et al., 2002). In this case, IL-2 was
genetically fused to a single chain Fv antibody targeting to a tumor surface
antigen Her2/neu. The efficacy of this approach to deliver cytokine con-
tinuously, as measured by sustained serum cytokine levels, was comparable to
established continuous infusion protocols of IL-2 (Mier et al., 2001). Therefore,
a sustained low dose of cytokine delivered by microencapsulated cells is a
feasible alternative to standard bolus infusions.
Other cytokine-related products such as interleukin-1 receptor antagonist (IL-
1Ra) has been delivered also from microencapsulated cells to treat an IL-1-
alpha-secreting fibrosarcoma in an animal model (Bar et al., 2004). The
rationale was to block the IL-1 receptor activation by its ligand IL-1 involved in
inflammation, tumor growth and metastasis. In addition to the reduction in
tumor growth with this treatment, significantly fewer blood capillaries and
inflammatory cells surrounding the implant were observed, resulting in

improved immune tolerance of the capsules.
Taken together, these first experiments established the feasibility of using
microencapsulated cells to deliver cytokines for cancer immunotherapy. They
have shown that the delivery of recombinant gene products for cancer therapy
via microencapsulation is a viable concept. The pleiotropic effects of cytokines,
however, are complex and their use must be mitigated by careful scrutiny. Some
cytokines will undoubtedly complement artificial cell technology better than
others, while some can contribute undesirable effects such as a heightened
inflammatory response (Cirone et al., 2002).

10.5.3 Delivery of tumor antigens in a vaccine strategy

Unlike cytokines, which may have varying biological consequences, vaccines
need not have any biological activity themselves but act only as targets that
ultimately elicit immunity. Although vaccination is a well-proven strategy, it has
been difficult to generate a vaccine against cancer. As cancer cells are derived
from a patient's own cells, it can be difficult to generate a selective immune
response to tumors. However, genetic instability and aberrant antigen expression
have provided opportunities to vaccinate against specific tumor markers (Coggin
et al., 2005; Lo et al., 2005).
Proof-of-concept experiments illustrating the effective delivery of vaccine
antigens via microencapsulation have been done, mostly by prolonging the
exposure of antigen to the subject by immuno-isolation of the vaccine in
biodegradable microcapsules. Such examples include vaccines against human T-
lymphotropic virus type-1 (Frangione-Beebe et al., 2000, 2001), malaria antigen
SPf66 (Rosas et al., 2002), human -amyloid for treatment for Alzheimer's
disease (Brayden et al., 2001), as well as Ole e 1 allergen derived from olive
pollen as an allergy vaccine (Batanero et al., 2003). This system has been shown
to be versatile and safe, providing long-lasting immunity, even after a single