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Table 1 The spectrum of available immunotherapies

From: Cancer immunotherapy: the beginning of the end of cancer?

Strategy Basic mechanism and major advantages Major disadvantages Reference
Cytokines
 IL-2 -Stimulates the host’s immune system -Low response rates -Significant risk of serious systemic inflammation [1]
 IFN-α -Stimulates the host’s immune system -Durable responses (from a small subset of melanoma patients) -Low response rates -High-dose toxicity [1]
Cell-based therapies
 Vaccines -Stimulates the host’s immune system -Minimal toxicity (e.g., sipuleucel-T) -Administered in the outpatient clinic -Lack of universal antigens and ideal immunization protocols lead to poor efficacy and response [6]
 Adoptive cellular therapy -Omits the task of breaking tolerance to tumor antigens -Produces a high avidity in effector T cells -Lymphodepleting conditioning regimen prior to TIL infusion enhances efficacy -Genetic T cell engineering broadens TIL to malignancies other than melanoma -Restricted to melanoma -Safety issues, serious adverse effects, and lack of long lasting responses in many patients -Requires time to develop the desired cell populations -Expensive [5, 27, 60, 6264, 6870]
Immune checkpoint blockade
 Anti-CTLA-4 monoclonal antibodies -Unleashes pre-existing anticancer T cell responses and possibly triggers new -Exhibits potent antitumor properties -Prolongation of overall survival -Only a relatively small fraction of patients obtain clinical benefit -Severe immune-related adverse events have been observed in up to 35 % of patients [5, 13, 76, 77]
 Anti-PD1 and anti-PD-L1 antibodies -Sufficient clinical responses which are often long-lasting -Therapeutic responses in patients within a broad range of human cancers -Reduced toxicity compared to anti-CTLA-4 antibodies -Only a relatively small fraction of patients obtain clinical benefit [2, 84, 90]
 Combination immunotherapy (immune checkpoint blockade as the backbone) -Improvement of anti-tumor responses/immunity -May lead to increases in the magnitude, frequency, and onset of side effects [9, 10]
  1. IL-2, Interleukin 2; IFN-α, Interferon-alpha; CTLA-4, Cytotoxic T lymphocyte-associated protein 4; PD1, Programmed cell death protein 1; TIL, Tumor infiltrating antibodies