Different types of immuno-oncology (IO) therapies are actively being investigated.1 When organized by mechanism of action (MOA), six classes of IO therapies can be described, including cell therapies, cancer vaccines, oncolytic viruses, T cell targeted immunomodulators, other immunomodulators and CD3-targeted bispecific antibodies.1
Cell therapies
Cell therapy offers the promise to cure or lessen the burden of a disease by transferring intact and healthy live cells in a patient’s body. It is an active area of research touching a wide range of diseases. Adoptive cell therapy (ADC) is an example of approved cell therapy in immuno-oncology. ADC or cellular immunotherapy is the use of a patient’s own immune cells to fight cancer. The cells are either re-infused into the patient as is after expansion to increase the count of tumor fighting immune cells or they can be engineered to be more efficient in recognizing and eliminating tumor cells. An example of ADC is CAR-T cell therapy.2
Cancer vaccines
Cancer vaccines may be prophylactic or therapeutic. Prophylactic cancer vaccines are administered to healthy individuals to prevent the development of cancer. Some examples of approved therapeutic cancer vaccines include the hepatitis B virus (HBV) vaccine to prevent the ultimate development of hepatocellular carcinoma (HCC) and the human papilloma virus (HPV) vaccine, which is used to prevent cervical cancer. Therapeutic cancer vaccines are administered to cancer patients to eradicate an already ongoing cancer by strengthening the ability of the patient’s immune system to fight the cancer.
Oncolytic viruses
The use of oncolytic viruses as cancer immunotherapy exploits the abilities of some well-recognized viruses to elicit immunogenic cell death. This allows the exposition of multiple tumor-associated antigens that were hiding from immune detection. They can then be processed for presentation to the immune system via activated mature dendritic cells. When numbers of virus genomes are high, immunological danger signaling through damage-associated molecular pattern (DAMP) and pathogen-associated molecular pattern (PAMP) receptors are activated. This activation state retargets the adaptive immune system, including cytotoxic CD8+ T cells and helper CD4+ T cells, towards the tumor, thus lifting local immunosuppression.
T cell targeted immunomodulators
Some examples of these therapies utilizing T cell-targeted immunomodulators include monoclonal antibodies against PD-1 or CTLA-4 and some emerging co-stimulatory molecules as targets for immunotherapy include 4-1BB and OX40.
Checkpoint blockade therapies inhibit the interaction between cognate receptors and their ligands. They include antibody drug conjugates, cytokine therapy, tumor-specific T cells and dendritic cell vaccines.
Immune modulators acting on other immune cells or the TME
Besides T cells, NK cells are also being explored as potential candidates for use in cell therapy based on several lines of evidence. Downregulation of HLA-I levels can induce NK cell-mediated killing through a “missing-self” recognition mechanism.3 The inhibitory mechanism includes killer immunoglobulin-like receptors (KIRs) and CD94/NKG2A, which can recognize major histocompatibility complex (MHC) class I molecules.
Other immunomodulators, including those agonists against toll-like receptors (TLR) or interferon-α/β receptor 1 (IFNAR1), are actively being investigated.
CD3-targeted bispecific antibodies
CD3-targeted bispecific antibodies (e.g., blinatumomab) are used to redirect naïve T cells and induce target cell–specific lysis.