Combining Targeted Nanomedicine and Cancer Immunotherapy View PDF

Abstract

Cancer immunotherapy can be improved significantly by nanomedicine. A nanomedicine is a drug delivery system with a size between 1-100 nm-sized used primarily for improving the efficiency and toxicity of conjugated or entrapped chemotherapy drugs. Clinical performance of cancer nanomedicines has been somewhat disappointing, primarily because there are no tools and technologies to stratify patients. Immunotherapy, on the other hand, has led to complete cures and long-term survival in patients with advanced stages of cancer. There are, however, relatively few patients who benefit from immunotherapy. There is increasing evidence that combing nanomedicine and immunotherapy can enhance therapeutic outcomes by making “cold” non-immunoresponsive tumors and metastases “hot” and immune-responsive. Three different approaches to nano-immunotherapy are available, in which nanomedicines are used to target cancer cells, the tumor immune microenvironment, and the peripheral immune system. Cancer cells are typically targeted with nanomedicines that induce immunogenic cell death, releasing tumor antigens and molecular patterns that indicate danger, such as calreticulin, high mobility group box 1, and adenosine triphosphate. By promoting the generation of CD8+ cytotoxic T cells, adjuvants alert antigen-presenting cells to take up, process, and present the former. As well as inhibiting immunosuppressive cells, such as M1-like tumor-associated macrophages, nanomedicines targeting the tumor immune microenvironment also inhibit the expression of immunosuppressive molecules, such as transforming growth factor beta, which potentiate cancer immunotherapy. Nanomedicines can also be used in the tumor immune microenvironment to promote the activity of antigen-presenting cells and cytotoxic T cells. By engineering and strengthening peripheral effector immune cell populations, nanomedicines targeting the peripheral immune system aim to enhance antigen presentation and cytotoxic T cell production in secondary lymphoid organs, such as lymph nodes and spleens, thus promoting immunity against cancer. Despite the fact that most immunomodulatory nanomedicines are still in preclinical development, early clinical trials have shown promising results. The right nanomedicine formulation must be combined with the right immunotherapy in the right patient in order to ensure efficient translation of nano-immunotherapy constructs and concepts. Nano-biomarker identification is currently underway, as are some immuno-biomarker initiatives, such as Immunoscore and Cancer Immunograms, which are partially established. This combination of protocols will enable the identification and use of individualized and improved nanomedicine-based treatments to boost the performance of cancer immunotherapy by capturing individual nano-immuno-statuses.

Keywords

Nanomedicine; Cancer; Immunotherapy