In the Journal of Controlled Release, Vol. 336, 2021, Islam A. Khalil's research group from the Misr University for Science and Technology (Egypt) published a review article titled "Cancer immunotherapy from biology to nanomedicine."

Cancer is one of the most common causes of mortality in humans, and treatments such as chemotherapy, radiation, and surgery all have therapeutic limitations and can result in tumor recurrence as well as various side effects. Immunotherapy is a relatively new and promising therapeutic method that has grown in popularity over the previous decade. Immunotherapeutic drugs (https://www.creative-biolabs.com/immuno-oncology/) focus on tumor-specific pathways, antigens, or biological targets to enable immune cells to and engage tumor cells, and they have been demonstrated to destroy tumor cells and prevent multidrug resistance (MDR) with fewer side effects than traditional cytotoxic medicines.

Checkpoint inhibitors, cytokines, monoclonal antibodies, and vaccinations are the four main categories of immunotherapeutic drugs, which, on the other hand, still have certain drawbacks, such as off-target effects and poor pharmacokinetic profiles.

Checkpoint Inhibitors
Immune checkpoints are immune system regulators that help the body maintain self-tolerance. They control the immune response to foreign antigens in order to protect surrounding healthy tissues from injury and to prevent immune cells from attacking their own cells by mistake. T cells are activated by the tumor necrosis receptor family and the immunoglobulin superfamily, while T cells are inhibited by the cytotoxic T lymphocyte-associated antigen 4 (CTLA 4) receptor and the programmed death ligand-1 (PD-L1) receptor. Cancer cells develop immune resistance by dysregulating immune checkpoints in order to bypass recognition and attack by the immune system. Immune checkpoint inhibitors enhance the killing effect of the immune system on tumor cells by inhibiting these regulatory pathways activated by tumor cells.

Cytokines
Cytokines were the first FDA-approved cancer immunotherapeutic agents. The three main types of cytokines used in clinical cancer therapy are interleukins, interferons, and granulocyte-macrophage colony-stimulating factor (GM-CSF).

Monoclonal antibodies (mAbs: https://www.creative-biolabs.com/immuno-oncology/antibody-discovery.htm)
With many FDA-approved drugs, the use of mAbs in cancer therapy is well established. Direct antibody action, immune-mediated cell death, and angiogenesis blockage at the tumor site are the three basic modes of action for mAbs. Of these, immune-mediated cell killing occurs through a variety of mechanisms, including complement-dependent cytotoxicity (CDC), antibody-dependent cytotoxicity (ADCC), and regulation of T-cell function.

Vaccines
Cancer vaccines can be divided into prophylactic and therapeutic vaccines. Typically, prophylactic vaccines target cancers caused by viral infections, several of which have been approved by the FDA, such as Cervarix® and Gardasil-9® for the prevention of human papillomavirus (HPV). The development of therapeutic vaccines is based on the selection of tumor-associated antigen (TAA) and tumor-specific antigen (TSA) overexpressed in tumor cells, construction of delivery systems targeting tumor cells, and selection of adjuvants to enhance the immune response. In addition, mRNA-based therapeutic vaccines can induce the generation of personalized immune responses against cancer cells and have strong application prospects.

The goal of the next generation cancer immunotherapies is to learn more about the tumor microenvironment and its immunosuppressive properties. Furthermore, in order to select the proper immunotherapy for diverse patient cases, a deeper understanding of tumor heterogeneity and other cancer-related biomarkers is required.

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