The pathotropic targeting of therapeutic nanoparticles to cancerous lesions is an innovative concept that has recently been reduced to practice in clinical trials for the treatment of metastatic
cancer. Previously, we reported that
intravenous infusions of Rexin-G, a pathotropic nanoparticle (or vector) bearing a cyto-ablative construct, induced
tumor regression, reduced
tumor burden, and improved survival, while enhancing the overall quality-of-life of patients with otherwise intractable
chemotherapy-resistant
cancers. In this report, we describe the major histopathological and radiologic features that are characteristic of solid
tumors under the destructive influences of Rexin-G administered as a single therapeutic agent. To further promote
tumor eradication and enhance
cancer survival, we explored the potential of an auxiliary gene transfer strategy, specifically intended to induce a localized
cancer auto-immunization in addition to assisting in acute
tumor destruction. This immunization strategy uses Rexin-G in combination with Reximmune-C, a
tumor targeted expression vector bearing a
granulocyte macrophage-colony stimulating factor (
GM-CSF) gene.
Intravenous infusions of Rexin-G were given first to induce apoptosis and
necrosis in the metastatic
tumor nodules, thus exposing
tumor neo-
antigens, followed by Reximmune-C infusions, intended to recruit immune cells discretely into the same compartments (or lesions). The intent of this two-step approach is to bring a
complement of cells involved in humoral and cell-mediated immunity in close proximity to the immunizing
tumor antigens in a concerted effort to assist in
tumor eradication and to promote a
cancer vaccination in situ. Herein, we also describe the distinctive histopathologic and immunocytochemical features of
tumors in terminal
cancer patients who received Rexin-G infusions in combination with Reximmune-C. In addition to documenting the first histological indications of clinical efficacy achieved by this novel personalized approach to
cancer vaccination, we discuss new methods and strategies for advancing its therapeutic utility. Taken together with the clinical data, these histological studies serve as valuable landmarks for medical oncology, and as definitive benchmarks for the emerging field of cancer gene
therapy.