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KEY POINTS
Cancer immunotherapy utilizing T cells to eliminate tumors has become the fifth pillar of cancer treatment alongside surgery, radiotherapy, chemotherapy, and targeted therapy.
Two major immunotherapeutic approaches to treat cancer include immune checkpoint blockade and adoptive T cell therapy with tumor-infiltrating lymphocytes and chimeric antigen receptors (CARs).
Immune checkpoint inhibitors (ICIs) can cause overwhelming inflammation and tissue damage, resulting in autoimmune-like toxicities known as immune-related adverse events (irAEs).
The most studied and targeted immune checkpoint receptors are programmed death-1 (PD-1), programmed death-ligand 1 (PD-L1), and cytotoxic T lymphocyte antigen-4 (CTLA-4).
The frequency and severity of irAEs are higher with anti-CTLA-4 alone and in combination therapy with anti-PD-1. Additionally, the most serious irAEs are pulmonary, neurologic, and cardiovascular toxicities.
The use of systemic corticosteroids and discontinuation of ICI is the mainstay of therapy for higher grade irAEs.
Cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) are the most common toxicities associated with CAR-T therapy.
Anticytokine therapy (eg, tocilizumab) and corticosteroids, in addition to supportive measures, are the mainstays of treatment of CRS.
Management of ICANS includes the use of corticosteroids, and control of seizures and cerebral edema in severe cases.
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Cancer immunotherapy has become a rapidly developing specialty in the field of oncology and has significantly improved survival and quality of life for patients while decreasing toxicity. Cancer immunotherapy utilizes the immune system to eliminate tumor cells and has become the fifth pillar of cancer treatment alongside surgery, radiotherapy, chemotherapy, and targeted therapy.
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The concept of cancer immunotherapy originated in the late 19th century with Wilhelm Busch and Friedrich Fehleisen, who first described the epidemiological association between immune status and cancer.1,2 They observed spontaneous regression of tumors following the development of erysipelas, a superficial skin infection most commonly caused by Streptococcus pyogenes. In 1891, William Coley, an orthopedic surgeon at Memorial Hospital in New York, showed long-term regression of inoperable sarcomas with intratumoral injections of live or inactivated Streptococcus pyogenes and Serratia marcescens (Coley’s toxins) in more than 1000 patients.3 It took more than half a century later, in the 1970s, for researchers to demonstrate the regression of cutaneous melanoma after intradermal injection of the bacterium Bacillus Calmette-Guerin (BCG) and the regression of metastatic melanoma in the bladder after intravesical administration of BCG.4 In 1976, Morales et al reported the first successful clinical trial of superficial bladder cancer treated with intravesical BCG.5
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The next key discovery in cancer immunotherapy came in the 1980s with better understanding of the process of immune surveillance, whereby innate immune cells, in particular T cells, eliminate cancer cells. This led to the approvals of other immunotherapeutic agents, including interferon-alfa and interleukin-2.1 Over the past two decades, the development of monoclonal antibodies (mAbs), immune checkpoint inhibitors (ICIs), and immune effector cell (IEC) therapy has revolutionized the treatment of cancer. Although these ...