The future of affordable cancer immunotherapy

Abstract

The treatment of cancer was revolutionized within the last two decades by utilizing the mechanism of the immune system against malignant tissue in so-called cancer immunotherapy. Two main developments boosted cancer immunotherapy: 1) the use of checkpoint inhibitors, which are characterized by a relatively high response rate mainly in solid tumors; however, at the cost of serious side effects, and 2) the use of chimeric antigen receptor (CAR)-T cells, which were shown to be very efficient in the treatment of hematologic malignancies, but failed to show high clinical effectiveness in solid tumors until now. In addition, active immunization against individual tumors is emerging, and the first products have reached clinical approval. These new treatment options are very cost-intensive and are not financially compensated by health insurance in many countries. Hence, strategies must be developed to make cancer immunotherapy affordable and to improve the cost-benefit ratio. In this review, we discuss the following strategies: 1) to leverage the antigenicity of "cold tumors" with affordable reagents, 2) to use microbiome-based products as markers or therapeutics, 3) to apply measures that make adoptive cell therapy (ACT) cheaper, e.g., the use of off-the-shelf products, 4) to use immunotherapies that offer cheaper platforms, such as RNA- or peptide-based vaccines and vaccines that use shared or common antigens instead of highly personal antigens, 5) to use a small set of predictive biomarkers instead of the "sequence everything" approach, and 6) to explore affordable immunohistochemistry markers that may direct individual therapies.

Keywords: RNA-based vaccines; adoptive cell therapy; affordable; biomarkers; immunohistochemistry; immunotherapy; microbiome.

Figure 1

Factors that contribute to the high costs of individualized medicinal products and possibilities for cost reduction. The production of cellular therapeutics usually takes place on a per-patient basis, i.e. each patient requires a personal small-scale production of the individualized medicinal product in a specialized facility under labor-intensive documentation. Source materials are usually patient-derived living cells, which increases the logistic effort. Next generation sequencing and other omics data are exploited to define individual antigens, which are synthesized in a personalized manner. Alternatively, therapeutic components could be produced at larger scale, increasing the economic efficiency, creating a warehouse of constituents. Using individual patient data, possibly exploited with the help of Artificial Intelligence (AI) to identify a manageable set of informative markers, an individual combination of these elements is selected to generate the individualized product. When possible, truly individual components are avoided or reduced to a minimum, including patient-derived cells. To improve the efficiency of the treatment further, the in depth data analysis can propose the use of established thus cheaper drugs in combination with the advanced individualized medicinal products. See the main text for further details. The Motifolio Scientific Illustration Toolkit was used for the generation of this figure.