Breakthrough of Cancer Immunotherapy

Breakthrough of Cancer Immunotherapy: Review

From 1960s, numerous progresses have been made in the area of cancer immunotherapy.
In the1960s and 70s,cancer immunotherapy was focused on intratumoral bacterial products or extracts such as Bacille Calmette-Guerin (BCG).
In the 1970s and 1980s, studies in cancer immunotherapy is about cancer vaccines with using whole autologous or allogeneic tumor cells. Lymphocyte subsets and cytokines such as interferons(IFN-α) and interleukin 2 (IL-2) that induced growth and activation of T cells and natural killer cells were discovered and introduced.
In 1990s, increased attention was given to the concept that effective immunotherapy was limited by regulatory mechanisms for controlling immune activation and an immunosuppressive tumor microenvironment. Several factors were implicated, including inhibitory ligand-receptor interactions that limited T-cell activation and function (CTLA-4), immunosuppressive cytokines (eg, transforming growth factor [TGF]-β, IL-4, IL-6, and IL-10), immunosuppressive cells (eg, T-regulatory cells [Tregs], myeloid-derived suppressor cells, and granulocytes), and cell signaling disruption (via class1 antigen loss, down-modulation of T-cell receptor [TCR] zeta chain expression, and indolamine dioxide secretion).
At the end of 20th century, Two clinical approaches, which entered the clinic within a short period of each other at the end of the century, heralded the new era of cancer immunotherapy. The first is tumor-infiltrating lymphocyte (TIL) therapy, and the second is substantial anti-tumor effects of blocking specific factors, most prominent the inhibitory ligand–receptor interactions, that served as physiologic brakes on the immune system.The CTLA-4 monoclonal antibody, receivec the US Food and Drug Administration (FDA) approval in 2011 for the treatment of patients with advanced melanoma. The broad clinical activity of anti–PD-1 and anti–PD-L1 energized thepharmaceutical and biotechindustry to initiate or expand preclinical and clinical research programs for cancer immunotherapy agents.
Now, combination immunotherapy is on the way to success.

Breakthrough of Cancer Immunotherapy: Reference

Atkins M B et al. Cancer Immunotherapy: Past Progress and Future Directions[C]//Seminars in oncology. Elsevier, 2015, 42(4): 518-522.
Morton DL et al.BCG immunotherapy of malignan tmelanoma:summary of a seven-year experience. AnnSurg.1974;180(4):635–43.