Trial watch

Consensus guidelines for the detection of immunogenic cell death

“…This is the case of cardiac glycosides including digoxin and digitoxin, which nonetheless are powerful at converting non-immunogenic instances of cell death into bona fide ICD, hence operating as a potent immune adjuvant. [95][96][97]235 Several assays are commercially available to monitor cell death-associated parameters, the most reliable indicator of cell death being end-stage plasma membrane permeabilization. 9,236 This can be monitored by so-called exclusion dyes like the DNAbinding chemicals propidium iodide (PI) and 4 0 ,6-diamidino-2-phenylindole (DAPI), which only accumulate in cells with permeabilized plasma membranes.…”

“…232 Moreover, cardiac glycosides were found to robustly improve the immunogenic potential of cell death. [95][96][97]235 We expect this platform not only to allow for the discovery of other ICD inducers, but also to facilitate the understanding of the molecular pathways that underlie ICD and how these can be modulated for therapeutic purposes.…”

“…93,94 In addition, some interventions are capable of converting non-immunogenic instances of cell death into bona fide ICD. These maneuvers include the administration of cardiac glycosides, which are particularly powerful in this respect as they promote per se all major manifestations of ICD (see below), [95][96][97] or zoledronic acid (a bisphosphonate currently approved to treat osteoporosis and to prevent skeletal fractures in cancer patients with bone metastases), 98,99 as well as the provision of co-stimulatory signals via CD40. 100 This said, it should be kept in mind that the capacity of a given agent to cause ICD or exacerbate the immunogenicity of apoptosis cannot be predicted yet from its structural or chemical properties, since molecules as similar to each other as oxaliplatin and cisplatin do not share this functional profile.…”

Trial Watch: Immunogenic cell death inducers for anticancer chemotherapy

“…58,59 However, for the reasons mentioned above, FDA-approved epothilones (i.e., ixabepilone, which is licensed for the treatment of breast carcinoma) 60 and EGFR-targeting mAbs (i.e., cetuximab and panitumumab, which are currently employed for the treatment of head and neck cancer and colorectal carcinoma) [61][62][63] may not share this ability with patupilone and 7A7, respectively. Finally, it should be noted that some FDA-approved agents such as digoxin and digitoxin (which are licensed for the treatment of various cardiac disorders), 64 as well as zoledronic acid (which is commonly employed for the treatment of MM or hypercalcemia and bone lesions of oncological origin), 65 are very efficient at boosting the immunogenicity of otherwise non-immunogenic instances of cell death, although they are unable to elicit ICD per se. [66][67][68][69] These agents may be particularly relevant for the development of combinatorial chemotherapeutic regimens that actively engage the host immune system against malignant cells.…”

Phytochemical Screening of Medicinal Plants of the Kakamega Country, Kenya Commonly Used against Cancer

“…Cardiac glycosides (CGs) are natural compounds that are potent inhibitors of the plasma membrane Na ions which can lead to myocardial contractility. CGs tends to exert potent antineoplastic effects by increasing the immunogenicity of dying cancer cells [31]. Digitoxigenin can be classified as a cardioactive steroid aglycone's prototype.…”