Abstract
Simple SummaryAdrenocortical carcinoma is a rare and life-threatening cancer originating from the adrenal glands. Although aggressive surgical interventions may cure this cancer when detected at early stages, treatments for advanced or metastatic disease are limited and often unable to shrink or control the growth of this tumor. Research into new treatments is needed for adrenal cortical carcinoma and other rare cancers. For cancers and other medical conditions, new therapies can be tested through clinical trials, in which patients are treated with new medications or innovative medication combinations. Among these novel and innovative treatments are immunotherapies. These therapies are playing an increasingly important role in the treatment of multiple different cancers. This article focuses on the various immunotherapies that have been, currently are, or will be tested in clinical trials for the treatment of adrenocortical carcinoma.Adrenocortical carcinoma (ACC) is a rare cancer of the adrenal gland that is frequently associated with excess production of adrenal hormones. Although surgical resection may be curative in early-stage disease, few effective therapeutic options exist in the inoperable advanced or metastatic setting. Immunotherapies, inclusive of a broad array of immune-activating and immune-modulating antineoplastic agents, have demonstrated clinical benefit in a wide range of solid and hematologic malignancies. Due to the broad activity across multiple cancer types, there is significant interest in testing these agents in rare tumors, including ACC. Multiple clinical trials evaluating immunotherapies for the treatment of ACC have been conducted, and many more are ongoing or planned. Immunotherapies that have been evaluated in clinical trials for ACC include the immune checkpoint inhibitors pembrolizumab, nivolumab, and avelumab. Other immunotherapies that have been evaluated include the monoclonal antibodies figitumumab and cixutumumab directed against the ACC-expressed insulin-like growth factor 1 (IGF-1) receptor, the recombinant cytotoxin interleukin-13-pseudomonas exotoxin A, and autologous tumor lysate dendritic cell vaccine. These agents have shown modest clinical activity, although nonzero in the case of the immune checkpoint inhibitors. Clinical trials are ongoing to evaluate whether this clinical activity may be augmented through combinations with other immune-acting agents or targeted therapies.
Highlights
Immuno-oncology is a rapidly expanding field of study focused on the interaction between the human immune system and malignancies, both hematologic and solid tumors, in the context of tumor initiation, proliferation, and progression
The first in vivo model of humanized Adrenocortical carcinoma (ACC) patient-derived xenograft (PDX) mouse has been reported [100]. This will allow for further investigation into the effect of immune checkpoint inhibitors in the preclinical setting and may open the doors to further explore the various modes of immunotherapy for ACC in experimental laboratory settings [100]
ACC is a rare malignancy with a dismal prognosis
Summary
Immuno-oncology is a rapidly expanding field of study focused on the interaction between the human immune system and malignancies, both hematologic and solid tumors, in the context of tumor initiation, proliferation, and progression Investigation in this field has resulted in the development of immunotherapies directed at unleashing the patient’s immune system to target and destroy cancerous cells. As a broad term inclusive of several immune-targeting strategies aimed at unleashing a patient’s own immune system against malignancies, immunotherapies are frequently subcategorized as either active or passive therapies. This distinction is based upon whether these therapies act through activation of the host immune system (active) or through antineoplastic activity intrinsic to the agent itself (passive) to target tumor cells. Multiple active and passive immunotherapies for adrenocortical carcinoma (ACC) have been and are actively under investigation at this time, and results of these studies are discussed in this review
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