Cancer Immunotherapy

Abstract

Cancer immunotherapy consists of approaches that modify the host immune system, and/or the utilization of components of the immune system, as cancer treatment. During the past 25 years, 17 immunologic products have received regulatory approval based on anticancer activity as single agents and/or in combination with chemotherapy. These include the nonspecific immune stimulants BCG and levamisole; the cytokines interferon-α and interleukin-2; the monoclonal antibodies rituximab, ofatumumab, alemtuzumab, trastuzumab, bevacizumab, cetuximab, and panitumumab; the radiolabeled antibodies Y-90 ibritumomab tiuxetan and I-131 tositumomab; the immunotoxins denileukin diftitox and gemtuzumab ozogamicin; nonmyeloablative allogeneic transplants with donor lymphocyte infusions; and the anti-prostate cancer cell-based therapy sipuleucel-T. All but two of these products are still regularly used to treat various B- and T-cell malignancies, and numerous solid tumors, including breast, lung, colorectal, prostate, melanoma, kidney, glioblastoma, bladder, and head and neck. Positive randomized trials have recently been reported for idiotype vaccines in lymphoma and a peptide vaccine in melanoma. The anti-CTLA-4 monoclonal antibody ipilumumab, which blocks regulatory T-cells, is expected to receive regulatory approval in the near future, based on a randomized trial in melanoma. As the fourth modality of cancer treatment, biotherapy/immunotherapy is an increasingly important component of the anticancer armamentarium.

RNA-binding protein nucleolin in disease

“…Interleukin (IL)-2 is a major cytokine implicated in the response against microbial infection and is used in certain cancer therapies. 42 Unlike nucleolin's binding to the 3' UTR of BCL2 and APP mRNAs, nucleolin binds the 5' UTR of IL2 mRNA, and this interaction is required for JNK-mediated IL2 mRNA stabilization during T-cell activation, likely in cooperation with the Y box-binding protein-1 (YB-1). 43 GADD45A mRNA.…”

Untitled

“…Blockade of constitutive CTLA-4 signaling in Tregs also potentiates response [83]. However, non-specific up-regulation of CTLs can lead to significant autoimmune adverse events [84]. A similar drug, the IgG2 mAb tremelimumab, is also under development [84].…”

“…However, non-specific up-regulation of CTLs can lead to significant autoimmune adverse events [84]. A similar drug, the IgG2 mAb tremelimumab, is also under development [84]. CTLA-4 checkpoint inhibitors have striking potential to release T-cell immune-suppression in HNSCC, where the immune microenvironment is characterized by CTL anergy and Treg infiltration.…”

Production of recombinant immunotherapeutics for anticancer treatment

“…9 Research on cancer vaccines has used several sources of tumor antigens, such as purified or synthesized tumor cell-surface molecules (proteins, peptides or lysates) and cells or lysates of allogeneic or autologous tumor cell lines. 10 Tumor-specific antigens (TSAs) could be a perfect target for cancer vaccines because these antigens are essential for tumorigenesis and cancer progression. In contrast, tumor-associated antigens (TAAs) are not specific and can be found in tumors with the same histology as well as in tumors of different origins and even in certain normal cells.…”